SMJ

E-ISSN 2228-8082

Volume 75, Number 2, February 2023

SPECIAL ISSUE

MONTHLY

Siriraj Medical Journal

The world-leading biomedical science of Thailand

ORIGINAL ARTICLE REVIEW ARTICLE

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Siriraj Medical Journal SMJ‌

Volume 75, Number 2, February 2023

ORIGINAL ARTICLE

62 A 30-year Patch Testing Experience at Siriraj Dermatology

Silada Kanokrungsee, et al.

70 Patch Testing of Thai Children with Eczema

Pailin Puangpet, et al.

76 Perception and Management Practice of Onychomycosis among Thai Physicians

Pichaya Limphoka, et al.

85 Clinical Features of Adult Male Acne in a Tropical Country: A Prospective Cross- sectional Study

Chayanee Likitwattananurak, et al.

92 Human-pet Relationship, Pet Abandonment, and Clinical Correlation for Patients Infected with Dermatophytosis of the Glabrous Skin

Sanchai Sombatmaithai, et al.

99 Association Between the Level of Inflammation at Each Anatomical Sexual Activity from Gram Staining and Neisseria gonorrhoeae and Chlamydia trachomatis Infections

Kittipoom Chinhiran, et al.

106 Prevalence and Trend of Photodermatoses in Thailand: A 16-year Retrospective Study in a Tertiary Care Hospital

Surachanee Likittanasombat, et al.

115 Validity and Reliability of the Topical Corticosteroid Phobia (TOPICOP©) Questionnaire: Thai version

Niorn Boonpuen, et al.

121 Diphenylcyclopropenone Treatment Outcomes for Alopecia Areata

Supenya Varothai, et al.

132 Evaluation of Hair Follicle Counts of Occipital Scalp Biopsies from Male Hair Transplant Patients in Thailand

Penvadee Pattanaprichakul, et al.

138 Histopathological Diagnosis of Alopecia Clinically Relevant to Alopecia Areata

Chinmanat Lekhavat, et al.

REVIEW ARTICLE

145 Direct Immunofluorescence in Cutaneous and Systemic Lupus Erythematosus: A Literature Review

Chuda Rujitharanawong, et al.

SMJ

SIRIRAJ MEDICAL JOURNAL

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Robin CN Williamson (Royal Postgraduate Medical School, UK) Tai-Soon Yong (Yonsei University, Korea)

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Tomohisa Uchida (Oita University, Japan)

Yoshiki Hirooka (Nagoya University Hospital, Japan)

Hidemi Goto (Nagoya University Graduate School of Medicine, Japan) Kazuo Hara (Aichi Cancer Center Hospital, Japan)

Shomei Ryozawa (Saitama Medical University, Japan) Christopher Khor (Singapore General Hospital, Singapore) Yasushi Sano (Director of Gastrointestinal Center, Japan) Mitsuhiro Kida (Kitasato University & Hospital, Japan) Seigo Kitano (Oita University, Japan)

Ichizo Nishino (National Institute of Neuroscience NCNP, Japan)

Masakazu Yamamoto (Tokyo Women’s Medical University, Japan) Dong-Wan Seo (University of Ulsan College of Medicine, Korea) George S. Baillie (University of Glasgow, UK)

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Sara Schwanke Khilji (Oregon Health & Science University, USA) Matthew S. Dunne (Institute of Food, Nutrition, and Health, Switzerland) Marianne Hokland (University of Aarhus, Denmark)

Marcela Hermoso Ramello (University of Chile, Chile) Ciro Isidoro (University of Novara, Italy)

Moses Rodriguez (Mayo Clinic, USA)

Robert W. Mann (University of Hawaii, USA)

Wikrom Karnsakul (Johns Hopkins Children’s Center, USA)

Frans Laurens Moll (University Medical Center Ultrecht, Netherlands) James P. Dolan (Oregon Health & Science University, USA)

John Hunter (Oregon Health & Science University, USA) Nima Rezaei (Tehran University of Medical Sciences, Iran) Dennis J. Janisse (Subsidiary of DJO Global, USA)

Folker Meyer (Argonne National Laboratory, USA)

David Wayne Ussery (University of Arkansas for Medical Sciences, USA) Intawat Nookaew (University of Arkansas for Medical Sciences, USA)

Victor Manuel Charoenrook de la Fuente (Centro de Oftalmologia Barraquer, Spain)

Karl Thomas Moritz

(Swedish University of Agricultural Sciences, Sweden)

Nam H. CHO (University School of Medicine and Hospital, Korea)

Watchara Kasinrerk (Chiang Mai University, Thailand)

Editorial Board

Pornchai O-Charoenrat (Siriraj Hospital, Mahidol University, Thailand)

Rungroj Krittayaphong (Siriraj Hospital, Mahidol University, Thailand) Wiroon Laupattrakasem (Khon Kaen University, Thailand)

Anuwat Pongkunakorn (Lampang Hospital, Thailand) Nopporn Sittisombut (Chiang Mai University, Thailand)

Vasant Sumethkul (Ramathibodi Hospital, Mahidol University, Thailand) Yuen Tanniradorm (Chulalongkorn University, Thailand)

Saranatra Waikakul (Siriraj Hospital, Mahidol University, Thailand) Pa-thai Yenchitsomanus (Siriraj Hospital, Mahidol University, Thailand) Surapol Issaragrisil (Siriraj Hospital, Mahidol University,Thailand) Jaturat Kanpittaya (Khon Kaen University, Thailand)

Suneerat Kongsayreepong (Siriraj Hospital, Mahidol University, Thailand)

Statistician: Saowalak Hunnangkul (Mahidol University, Thailand)

Nopphol Pausawasdi (Siriraj Hospital, Mahidol University, Thailand) Supakorn Rojananin (Siriraj Hospital, Mahidol University, Thailand) Jarupim Soongswang (Siriraj Hospital, Mahidol University, Thailand) Suttipong Wacharasindhu (Chulalongkorn University, Thailand) Prapon Wilairat (Mahidol University, Thailand)

Pornprom Muangman (Siriraj Hospital, Mahidol University, Thailand)

Ampaiwan Chuansumrit

(Ramathibodi Hospital, Mahidol University, Thailand)

Sayomporn Sirinavin

(Ramathibodi Hospital, Mahidol University, Thailand)

Vitoon Chinswangwatanakul

(Siriraj Hospital, Mahidol University, Thailand)

Medical Illustrator: Chananya Hokierti (Nopparat Rajathanee Hospital, Thailand)

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A 30-year Patch Testing Experience at Siriraj Dermatology

Silada Kanokrungsee, M.D., Pichanee Chaweekulrat, M.D., Chayada Chaiyabutr, M.D., Suthasanee Prasertsook, M.D., Chudapa Sereeaphinan, M.D., Monthathip Bunyavaree, B.Sc., Titinun Kumpangsin, B.Sc., Janista Thumrongtharadol, B.Sc., Waranya Boonchai, M.D.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: To identify trends of contact allergy and patch testing amendments at the Contact Dermatitis Clinic, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University.

Materials and Methods: Medical records of 6,862 patients referred to our clinic between January 1992 and December 2021 for patch testing were reviewed.

Results: The number of patients patch tested increased and reached a peak of 600 patients/year in 2019 before the COVID-19 pandemic. The most frequently used series was baseline, while the most used specific series was cosmetics. The overall positivity rate was 69%. The highest positivity rate was in the cosmetics series (70.2%). Nickel sulfate was the most common contact allergen found (24.2%).

Conclusion: Our patch test service has been growing in the last 30 years. The series of allergens used for patch testing has been amended every few years to be up-to-date with current global trends of contact allergies. Continual surveillance of contact prevalence and periodic updating of those series are necessary to enhance our ability to detect culprit contact allergens, which could help us improve care of our patients.

Keywords: Patch test; contact dermatitis; Siriraj; contact allergens; skin allergy; Thailand (Siriraj Med J 2023; 75: 62-69)

INTRODUCTION

Allergic contact dermatitis (ACD) is a common skin disease caused by immunological hypersensitivity to particular substances. Patch testing is considered the gold standard diagnostic procedure for identifying specific allergens that cause contact skin allergies. The baseline allergens, which contain common contact allergens found in certain populations is recommended for patch testing in every patient.1 Furthermore, additional series are selected and used in testing based on a patient’s rash and exposure history.2 Specific allergens in each patch test series are updated, depending on the current trends of allergenicity at that time.3

History

Patch tests were introduced as a diagnostic tool for ACD in the late nineteenth century by German physician Joseph Jadassohn.4 Contact Dermatitis Clinic, at Siriraj Hospital was established by Clinical Professor Emeritus Patcharee Sunthonpalin, M.D., who wrote the first and only Contact Dermatitis textbook in Thai. The clinic has been in operation since 1972 under the Department of Medicine, Faculty of Medicine Siriraj Hospital. The clinic started with six allergen series, including baseline, cosmetic, fragrance & botanical, textile, photoallergen & sunscreen, and the hair series. In 2010, our clinic hired more staff and expanded its services. In 2013, the name

Corresponding author: Waranya Boonchai E-mail: waranya.boonchai@gmail.com

Received 10 June 2022 Revised 27 June 2022 Accepted 6 July 2022 ORCID ID:http://orcid.org/0000-0002-6673-6534 https://doi.org/10.33192/smj.v75i2.260755

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

of clinic was changed to the Occupational and Contact

Statistical analysis

Original Article SMJ

Dermatitis Clinic to broaden the range of disease focus. Since this time, many studies have been published in various international academic journals. There has also been improvement in our services, such as the creation of a own Nickel spot test (dimethylglyoxime),5 cobalt test,5 skin marking pen, Thai mite allergen for patch testing and a Thai database of Contact Allergen Avoidance Program or CAAP,5,6 in accordance with Mahidol University’s “Wisdom of the Land” to promote higher education and help society achieve a better quality of life. Currently, we have over 30 years of experience providing patch testing and treating contact and occupational-related dermatitis. Nowadays, we are the standard referral center for patch testing, and seventeen kinds of allergen series are available.7

As this year is the 30th anniversary of the founding of the Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, we aimed to publish the outcomes and trends of patch testing in our clinic over its history to celebrate this memorable achievement.

MATERIALS AND METHODS

Study design and participants

Retrospective charts between January 1992 and December 2021 were reviewed at the Occupational and Contact Dermatitis Clinic, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. Patients’ characteristics and patch test results were collected. This study was approved by the Siriraj Institutional Review Board (COA no. Si 808/2021).

Patch testing was carried out according to guidelines by the International Contact Dermatitis Research Group.8 The allergens (Chemotechnique Diagnostics, Vellinge, Sweden) in aluminium Finn Chambers (SmartPractice, Phoenix, Arizona) were applied on the patients’ upper back for 48 hours. The dermatologists measured the readings on day 2, 4 and 7, and the reaction was scored according to the guideline. Siriraj baseline series were adapted from the International standard and European baseline series.7,9 Some patients were tested with additional series such as the cosmetics series, and hairdressing series, depending on patients’ clinical histories.

Some series were not universally available at that period of time such as pigmented series that composed of 24 allergens; 13 allergens are allergen from baseline series such as paraphenylenediamine, fragrance etc. plus 11 particular allergens were jasmine oil, Ylang-ylang oil, benzyl salicylate, ammonium mercury, sudan I, disperse orange 3, disperse yellow 3, hydroquinone, coal tar, tricosan, and tretinoin. These allergens had been reported causing hyperpigmentation.

PASW Statistics for Windows, version 18 (SPSS Inc., Chicago, IL, USA), was used for data analysis. Categorical data was described using frequency and percentage. Continuous data was reported using mean and standard deviation for data with normal distribution or median and interquartile range for data with non- normal distribution.

RESULTS

Our clinic performed patch tests on a total 6,862 patients over a 30-year period. Most patients were female (78.6%), and the median age was 40 (29.0, 52.0) years old. Also, most patients were 18 – 59, or of working-age. Personal and family history of atopy was found in 42% and 32% of cases, respectively. Almost 40% of patients had a history of metal allergy, while only 15% had history of cosmetic allergy (Table 1).

The average number of patients who underwent patch testing was 229 (±158) patients/year. Between 1992 and 2006, the number of patients tested was approximately 100 patients/year, before it rose to almost 600 patients/ year in 2019 (Fig 1). However, the number of patients tested decreased in 2020 and 2021 due to the COVID-19 pandemic. The positivity rate was 69%, and it ranged between 60% and 90% each year. Table 2 shows all positivity rates of each series in five-year intervals over the 30-year study period.

The most frequent additional allergen series used besides the baseline over the 30-year period were cosmetics, cheilitis and hairdressing in 1,203 (17.5%), 493 (7.2%) and 292 (4.3%) patients, respectively. The positivity rate varied in each series over time (Table 2). The cosmetic series had the highest positivity rate of 70.2%, and at times reached as high as 80%, followed by melasma (66.7%), baseline (66.5%) and pigmented cosmetic series (65.1%).

Regarding allergens in the baseline series, the one with the highest positivity rate over 30 years was nickel sulfate (24.2%), followed by gold sodium thiosulfate (19.9%), linalool hydroperoxide (13.0%) and fragrance mix I (12.95%). The top three most common allergens during each five-year period were three metals (nickel, gold sodium thiosulfate, potassium dichromate), two fragrances (fragrance mixed I, linalool hydroperoxide) and two preservatives (paraben mix, methylisothiazolinone) as displayed in Fig 2. Common sensitizers throughout the course of the study are summarized in Fig 2. The constant rate of nickel was approximately 20-30%, with the highest clinical relevance rate at 83.23% over the past 30 years. Fragrance allergens, including fragrance mix I, mix II and balsum of Peru gradually decreased after

*, Blue-collar worker refers to workers who engage in hard manual labor, typically agriculture, manufacturing, construction, homemaker, mechanic, maintenance, or another physically exhausting task that implies belonging to a lower social class.

τ,White-collar workers are known as suit-and-tie workers who often avoid physical labor which implies belonging to a higher social class

Fig 1. Number of patients referred for patch testing and percentage of positive reactions between 1992 and 2021.

Original Article SMJ

TABLE 2. Positive patch test results in each patch test series.

https://he02.tci-thaijo.org/index.php/sirirajmedj/index Volume 75, No.2: 2023 Siriraj Medical Journal 65

Fig 2. Common allergens in baseline series between 1992 and 2021.

2002, however, linalool hydroperoxide, a new fragrance allergen, had a high percentage of positive reactions and was a top three most common allergen in the last five years. Regarding preservative allergens, the paraben mix showed a high positivity rate in the early period of the study period (1992-1997), but it later declined. In contrast, isothiazolinone, including methylchloroisothiazolinone/ methylisothiazolinone (MCI/MI) and methylisothiazolinone (MI), saw a gradual rise in positive reactive rate, and a slight decrease after 2016.

DISCUSSION

This retrospective study uncovered big changes in the patch testing process, and allergen series over a 30- year period at the Occupational and Contact Dermatitis Clinic, Siriraj Hospital. We noticed growth in patch testing services along with changes in contact sensitizers over time. The number of patients referred for patch testing per year has progressively increased year-on-year, with a remarkable rise since 2006, and a five to six-fold increase in 2019. We believe the growth of our clinic is the result of several support systems such as our departments and faculties, along with ongoing encouragement of referring

patients suspected of having ACD for patch testing. However, patch testing numbers decreased abruptly due to the COVID-19 outbreak from early 2020, like the rest of the world.10

The rate of positive patch test results in the baseline series, which are the standard set of allergens used in almost every patients suspected of having ACD in our clinic, was 66.5%, which is consistent with studies from the United states and Saudi Arabia as well as our previous study covering 2006-2018.11-13 We also noticed a decline in the percentage of reactions after 2006, which coincided with an increase in the number of patients tested. This could be due to the fact that there were more patients interested in getting tested and that we were less stringent on which patients to include. There are discrepancies in patch testing positivity worldwide, ranging from 22%-55%.14-16 This variation in positivity may be due to different exposures linked to local culture, industries, and regulations in each country. Furthermore, individual factors and the patch testing method are influential factors on the outcome as well.17

A chronological change in our contact allergen series was established around the world. Sensitizing allergens

in each patch test series were updated based on the current trends in allergenicity at that time.3 Many sets of allergens are available in our clinic, and each series differs in number of substances. The cosmetic series is the second most common, after following baseline series, but it generated the highest yield. In addition, the percentage of positive results from the cosmetic series has been gradually rising. Despite a slightly downward trend in the last five years, it is worth using in patients suspected of having ACD because ninety percent of cosmetic products in the Thai market contain at least one allergen.18 High rates of sensitization also reflect the growth of the cosmetic business and wide use of cosmetic products in our country. The melasma series was second, but it was only used between 2002-2004. Later, its allergens were merged into the cosmetic and pigmented series. Although reactions to the pigmented series have been declining, it remains the series with the fourth highest positivity rate. These findings suggest that although the baseline series already include common allergens from a specific time period, the addition of specialty allergen series relating to personal history or work products is still necessary for a complete evaluation, to increase the success rate of identifying the culprit, and to improve management of patients’ allergic contact dermatitis.11,19 However, the other series, such as, photoallergen, corticosteroid, plastic & glue, textile, oil & cooling and shoe, which have a small positivity rate, are more of a concern. This may indicate an inadequate set of allergens, which warrants a review.

Regarding individual allergens, nickel sulfate is known as the most common allergen worldwide.11,20-22 Its prevalence in this study was steady over the time and comparable with a previous study from Thailand (24.0% in 2006-2018 vs 27.6% in 2000-2009).9,21 However, the current study revealed a much higher share of positive reactions (24.2%) to nickel sulfate than studies from other Asian and European countries (13.9-20.4%).11,14,22-24 A declining trend was noted in European countries following nickel regulations and introduction of novel substitute metals,24 which contradicts results from our Thai study where there are no regulations on the specific amount of nickel allowed in nickel-containing accessories in the market.5 The allergens, which displayed a downward trend in our study, include cobalt, gold sodium thiosulfate, fragrance mix I and II, Myroxylon pereirae and parabens, which were potent sensitizers in the past. This can potentially be explained by a decline in exposures to these sensitizers. Furthermore, many industries have substitutes to avoid this problem, resulting in relatively less prevalence.

For allergens showing more prevalence, hydroperoxide of linalool has been an emerging allergen since 2020. Linalool is the most common fragrance material in cosmetic products sold in the European market and has been increasingly responsible for contact allergy in Europe.25 Our data showed that a positive reaction occurred in 13% of cases, compared to prior reports which reported a positivity rate ranging from 1.7-20%.11,26,27 The variation depends on the exposure rate of the individual country, the popularity of the allergen in the environment, regional legislation, and the population tested. An increase in MCI/MI was also noted. MI is isothiazolinone preservative mainly used in cosmetic and personal care products. High concentrations of MCI/MI and MI caused a global epidemic in the mid- 2010s.21,28-30 Consequently, for leave-on cosmetics, the use of MCI/MI and MI as an ingredient in Europe has been banned since 2016 and 2017,31,32 respectively, and the concentration of MI in rinse-off cosmetics has reduced since 2018 by the European Commission.33 According to the legislation, the prevalence of isothiazolinone allergy considerably decreased after 2016. The change in MCI/ MI and MI allergies in our study will likely follow global data as the Thai FDA usually takes a few years to adopt EU regulations.34,35

Limitation of our study was incomplete data due to long retrospective nature of study design e.g. clinical relevance of positive reaction information. Moreover, the study originated from single tertiary centre in Bangkok, Thailand, leading to lack of regional generality.

Siriraj Contact Dermatitis Clinic has been in operation for 30 years. This study reviewed 30-year outcomes at the clinic. Our patch testing service has grown over this period. The series of allergens used for patch testing is amended every few years to update it to the latest global trends of contact allergies. Continual surveillance of contact prevalence and periodic updates are necessary to enhance our ability to detect culprit contact allergens, and improve care of our patients.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge Assistant Professor Dr.Chulaluk Komoltri for statistical advice and support.

Conflicts of interest: All authors have no conflicts of interest or financial support to declare.

Funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit-sectors.

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30. Uter W, Aalto-Korte K, Agner T, Andersen KE, Bircher AJ, Brans R, et al. The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures. J Eur Acad Dermatol Venereol. 2020;34(2):333-9.

31. The European Union Commission. Commission Regulation (EU) No 1003/2014 of 18 September 2014 amending Annex V to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products. 2014. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF

    /?uri=CELEX:32014R1003&from=FR.

32. The European Union Commission. Commission Regulation (EU) 2016/1198 of 22 July 2016 amending Annex V to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products. 2016. Available from: https:// eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX

    :32016R1198&from=FR.

33. The European Union Commission. Commission Regulation (EU) 2017/1224 of 6 July 2017 amending Annex V to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products. 2017. Available from: https://

    eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX

    :32017R1224&from=EN.

34. Sukakul T, Limphoka P, Boonchai W. Methylchloroisothiazolinone and/or Methylisothiazolinone Contact Allergies in Thailand. Dermatitis. 2021;32(6):375-80.

35. Sukakul T, Kanchanapenkul D, Bunyavaree M, Limphoka P, Kumpangsin T, Boonchai W. Methylchloroisothiazolinone and/or methylisothiazolinone in cosmetic products-A market survey. Contact Dermatitis. 2019;80(2):110-3.

Patch Testing of Thai Children with Eczema

Pailin Puangpet, M.D.*, Niorn Boonpuen, M.D.*, Kasira Saipornchai, M.D.*, Pattarida Poompakdeepan, M.D.*, Rungrat Suchaoin, M.D.*, John McFadden, M.D.**

*Occupational and Contact Dermatology Clinic, Institute of Dermatology, Bangkok, Thailand, **St John’s Institute of Dermatology, King’s College, London, UK.

ABSTRACT

Objective: To detect contact allergy rate and common allergens in Thai children presented with eczema. Materials and Methods: A total of 124 children, aged 1-15 years, were patch tested using a pediatric screening series of 16 allergens and relevant additional allergens. Data on clinical presentation, atopic history and test results were collected.

Results: Contact allergy was found in 51 of 124 children (41.1%) presented with all forms of eczema. The common allergens were lanolin alcohol (8.9%), cocamidopropyl betaine (8.1%), nickel sulfate (7.3%), fragrance mix I (5.6%), formaldehyde (5.6%), thimerosal (5.6%), fragrance mix II (4.8%), cobalt chloride (4.0%), methylchloroisothiazolinone/

methylisothiazolinone (2.4%), methylisothiazolinone (2.4%) and thiuram mix (2.4%). Nineteen of 50 atopic dermatitis patients (38%) showed positive patch test reactions.

Conclusion: Allergic contact dermatitis is common in children. Both atopic and non-atopic patients can develop contact dermatitis. Patch testing should be performed in children presented with eczema regardless of contact dermatitis history.

Keywords: Patch test; children; pediatric; eczema; allergic contact dermatitis (Siriraj Med J 2023; 75: 70-75)

INTRODUCTION

Allergic contact dermatitis (ACD) is a cell-mediated hypersensitivity (type IV) reaction of the skin. The prevalence of ACD increases with age. Both ACD and irritant contact dermatitis in children seems to be important problems over the last years. The diagnosis of ACD is obtained with history, physical examination, and patch testing. The dermatitis observed can be both flare of the existing dermatitis and difficult-to-treat eczema. The location may be not only the direct contact sites, but also distal skin areas from ‘secondary spread’.

From a systematic review, studied the data from January 1997 to May 2012, the common allergens in children and adolescents were nickel, thimerosal, cobalt, fragrance mix I, lanolin, neomycin, potassium dichromate and Myroxylon pereirae.1 Frequent sources of allergens in children and adolescents are fragrances, creams, makeup,

toys, hair dyes, nail polish, henna tattoos, and piercings. Therefore, the sensitization rate among these age groups can be significantly rising.1 Previous studies showed prevalence rates of 13.3-24.5%.2

Nowadays, there is a wide selection of personal products that are used by children. Beauty trends in teenagers depend on cultures, social media, and influencers. Children and teenagers use cosmetics earlier and more than in the past. The contact allergens at present may not be the same.

Patch testing is an uncomfortable procedure for both children and parents. At least 3 visits are needed and patients have to avoid water on the patch test sites. These inconvenient factors might cause the clinicians being reluctant to refer patients for patch testing. Moreover, ACD can be easily misdiagnosed particularly in children who have existing atopic dermatitis. Patch testing is the

Corresponding author: Pailin Puangpet E-mail: pailin.samutrapong@gmail.com

Received 31 July 2022 Revised 31 August 2022 Accepted 4 October 2022 ORCID ID:http://orcid.org/0000-0002-3993-6434 https://doi.org/10.33192/smj.v75i2.260740

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

gold standard to identify this hidden second diagnosis. If the patients appropriately avoid the causative contact allergens, the recalcitrant dermatitis can improve leading to better quality of life.3

The aims of this study were to detect the frequency of contact sensitization in Thai children diagnosed with all forms of eczema regardless of the contact dermatitis history and to find the common contact allergens.

MATERIALS AND METHODS

This prospective study was conducted at the Occupational and Contact Dermatitis Clinic, Institute of Dermatology, Bangkok, Thailand over 19 months. Children, aged 1-15 years, diagnosed with all forms of eczema for more than 1 month were enrolled. Children who have contraindication to patch test procedure such as active widespread eczema or taking oral corticosteroid were excluded. Demographic data: age, sex, triggered factors, history of atopy, location and duration of lesions were recorded.

All patients were patch tested with the pediatric screening series of 16 allergens. (Table 1) Screening allergens, provided by AllergEAZE®, in AllergEAZE patch test chamber® and supplemental relevant allergens (in selective cases), provided by Chemotechnique Diagnostics, Sweden, were applied on the upper back. Patch test results were interpreted at day (D) 2 and D4 according to International Contact Dermatitis Research Group (ICDRG) criteria. The number of positive patch test reactions and clinical relevance were recorded.

RESULTS

One hundred and twenty-four children, 61 females and 63 males, were included. The average age was 8 years. Forty-eight cases (38.7%) were 1–7 years old, 76 cases (61.3%) were 8-15 years old. The mean duration of eczema before patch testing was 28.5 months (1-144 months). The mean recurrent episodes of eczema flares were 5 times per year. The legs and arms were the most common site involved (Table 2). The most commonly reported trigger factors in subjects with positive patch test reaction were heat, dust, and seafood. Insomnia was reported by 20.2% of cases.

The results showed 84 positive patch test reactions in 51 patients (41.1%). Current or past relevance was detected in 18 of 75 positive patch test reactions (24%). Lanolin alcohol was the most common contact allergen in our cohort, followed by cocamidopropyl betaine, nickel sulfate, fragrance mix I, formaldehyde, thimerosal, fragrance mix II, cobalt chloride, methylchloroisothiazolinone/ methylisothiazolinone (MCI/MI), methylisothiazolinone (MI) and thiuram mix. (Fig 1 and Table 3) There were 21 irritant patch test reactions from cocamidopropyl betaine, formaldehyde, cobalt chloride, MI, potassium dichromate and MCI/MI.

The additional relevant positive allergens found in 9 patients were house dust mite, benzalkonium chloride, an unknown topical corticosteroid cream and personal care products. Ten patients were patch tested with house dust mite allergen and 5 patients had a positive result (50%).

TABLE 1. Pediatric baseline series.

Substances Concentration and vehicle

Nickel sulfate 2.5 % Petrolatum

Balsam of peru 25 % Petrolatum

Fragrance mix I 8 % Petrolatum

Fragrance mix II 14 % Petrolatum

p-tert-Butylphenol formaldehyde resin 1 % Petrolatum

Formaldehyde 1% Water

Colophony 20 % Petrolatum

Potassium dichromate 0.25 % Petrolatum

Cobalt (II) chloride 1 % Petrolatum

Thimerosal 0.1 % Petrolatum

Lanolin alcohol 30 % Petrolatum

Methylchloroisothiazolinone/methylisothiazolinone 0.02 % Water

Methylisothiazolinone 0.2 % Water

Cocamidopropyl betaine 1 % Water

Thiuram mix 1 % Petrolatum

Mercapto mix 2 % Petrolatum

TABLE 2. Anatomic sites of involvement.

In addition, two or more positive allergic reactions were found in 24 children (19.4%). Of these, 7 patients had positive reaction to 3 allergens and 1 patient had positive reactions to 4 allergens (formaldehyde, thimerosal, nickel and personal product).

History of atopic dermatitis was presented in 50 of 124 subjects (40.3%), followed by allergic rhinitis (35.5%), asthma (3.2%) and allergic conjunctivitis (1.6%). Among patients with positive patch test reaction, allergic rhinitis and atopic eczema were found in 48.7% and 46.1% respectively. According to family history, allergic rhinitis was found in 46.8%, followed by atopic dermatitis 15.3%, asthma 8.1% and allergic conjunctivitis 5.6%.

Among 50 children who had atopic dermatitis history, 19 cases (38%) showed at least one positive patch test reactions. The common contact allergens in atopic dermatitis group were nickel (15.8%), lanolin alcohol (15.8%), cocamidopropyl betaine (10.5%).

DISCUSSION

ACD in children has been estimated as being uncommon. This study shows that contact sensitization

TABLE 3. Patch test reactions in children with eczema (N=124).

Fig 1. Percentage of positive patch test reactions in 124 children with eczema.

was found in 51/124 children (41.1%) corroborating the results reported in a study from the UK which has shown the prevalence of positive patch test reaction in 110 children with eczema aged 2-18 years to be 44%.4 The rates were 59.2% of 125 children and 51% of 79 children in Brazil and The Netherlands respectively.5,6 Patch test reaction rate in current study is lower

than the literature that revealed 26.6-95.6%.6 The reported clinical relevance of 51.7-100%7 was also higher than the in this study (24%). This could be because our study carried out in unselected children with eczema regardless of contact dermatitis history while most previous studies performed in patients suspected ACD and tested a larger number of allergens than in this study. Zug et al. reported 62.3% positive patch test results in North American children aged 18 years or younger during 2005 and 2012. These patients were suspicious of ACD and were patch tested with up to 70-allergen series.8

Our results highlight the significance of patch testing as an investigation of a child with chronic atopic dermatitis. Contact allergy coexists in 38% of children with atopic dermatitis (AD), most commonly to nickel sulfate (15.8%). Cattani et al.9 recently patch tested 54 Brazilian children, 4 -18 years old, with recalcitrant atopic dermatitis, positive reactions were found in 27.7%, most commonly to nickel sulfate, disperse blue, and fragrance mix I. ACD occurrence in children with atopic eczema

can be described by the impaired epidermal barrier that could enhance allergen penetration and the exposure to sensitizing chemicals in personal care products.10 Boonstra et al. reported that concomitant contact dermatitis may be a cause of AD becoming a difficult-to-treat disease.11 A retrospective study by Boonchai et al. showed a positive patch test reaction rate of 35.5% among 112 Thai children, aged less than 18 years, suspected ACD. The common allergens were nickel, potassium dichromate, methylisothiazolinone. These results may not be used to compare with our study because there are many differences in the study methodology: retrospective chart review vs prospective study, mean ages (14.5 vs 8 years), inclusion criteria (suspected ACD vs all forms of eczema) and the allergens routinely tested that did not include our common allergens such as cocamidopropyl

betaine and thimerosal.12

In this study, the most common allergen was lanolin alcohol. Exposure to lanolin can come from emollients, ointments, cosmetics, toiletries and topical medicaments.7 In a previous study in North America, prevalence of lanolin allergy was 4.6%.13 The results of TRUE (Thin-layer Rapid Use Epicutaneous Test showed lanolin allergy rate of 15.8% in 101 children and adolescents aged 6-18 years who were patch tested on suspicion of having ACD.14 Lanolin allergy was reported being more common in children than in adults (4.5% vs 3.2%).9 In our center,

the sensitization rate of lanolin alcohol in all age group including adults is approximately 1.5%. However, Uldahl et al. reported that patients allergic to lanolin may use lanolin-containing products on intact skin without problem15, but may develop allergic contact dermatitis after applying lanolin-containing topical medicaments to damaged or ulcerated skin. This phenomenon is called ‘lanolin paradox’. The difficulty in determining clinical relevance of a positive patch test reaction can cause by lanolin paradox. Moreover, it can be difficult to distinguish between true allergic reactions and irritant reaction.

Exposure sources of cocamidopropyl betaine include shampoos, cleansers, toothpaste, detergents, liquid soaps, bath gels, skin care products and antiseptics.16 Cocamidopropyl betaine was noted to be an important allergen in younger age group.17 In a retrospective study of 1142 children aged less than 18 years, there was a higher frequency of positive patch test reactions to cocamidopropyl betaine in patients with AD when compared to non-AD group.18

Nickel was high in our child cohort (7.3%). Most previous studies reported that nickel is the most common allergen causing ACD in children.5,6,7,19 Sensitization to nickel may begin in infancy. One patient was related to wearing necklace with metal sacred pendant amulet since birth. It is also a common practice to pierce ears at a very young age in Thailand, especially in girls.

One of our cases presented with upper lip dermatitis. Patch test revealed positive reactions to fragrance mix I, fragrance mix II and Myroxylon pereirae which possibly present in her favorite bottled soft drink. Very young children can be sensitized to contact allergen such as fragrance. Apart from direct contact in relation to the use of perfumed products, airborne contact of volatile perfume used by a family member can cause recurrent eyelid dermatitis. The mother of a young child bought a flameless stone burner that heats and diffuses aromatic oils containing fragrance in order to clean air in the home. Eyelid dermatitis improved after the mother stop using the burner. However, airborne dermatitis recurred when the child’s grandmother used perfume on herself in the same room.

A 7 year-old atopic boy presented with recalcitrant conjunctivitis and photophobia showed a relevant positive patch test to benzalkonium chloride. Benzalkonium chloride is a preservative in several eye medicaments for allergic conjunctivitis. Avoidance of benzalkonium chloride containing eye drops resulted in dramatic improvement.

CONCLUSION

This study indicates that allergic contact dermatitis is common in children. Lanolin, cocamidopropyl betaine and nickel are the top three common contact allergens in Thai pediatric population. Both atopic and non-atopic patients can develop contact dermatitis. Patch testing should be performed in children presented with eczema regardless of contact dermatitis history.

Limitation

The small number of allergens in our pediatric screening series could partly decrease the sensitivity of patch test. Further study testing with larger number of screening allergens for children is recommended.

REFERENCES

1. Rodrigues DF, Goulart EM. Patch-test results in children and adolescents: systematic review of a 15-year period. An Bras Dermatol. 2016;91(1):64-72.

2. Pigatto P, Martelli A, Marsili C, Fiocchi A. Contact dermatitis in children. Ital J Pediatr. 2010;13;36:2.

3. Kasemsarn P, Boonchai W. Usefulness of Patch Testing in Dermatology. Siriraj Med J. 2012;64(2):73-7.

4. Moustafa M, Holden CR, Athavale P, Cork MJ, Messenger AG, Gawkrodger DJ. Patch testing is a useful investigation in children with eczema. Contact Dermatitis. 2011;65:208-12.

5. Rodrigues DF, Goulart EM. Patch test results in children and adolescents. Study from the Santa Casa de Belo Horizonte Dermatology Clinic, Brazil, from 2003 to 2010. An Bras Dermatol. 2015;90(5):671-83.

6. de Waard-van der Spek FB, Oranje AP. Patch tests in children with suspected allergic contact dermatitis: a prospective study and review of the literature. Dermatology. 2009; 218:119-25.

7. Simonsen AB, Deleuran M, Johansen JD, Sommerlund M. Contact allergy and allergic contact dermatitis in children - a review of current data. Contact Dermatitis. 2011;65(5):254-65.

8. Zug KA, Pham AK, Belsito DV, DeKoven JG, DeLeo VA, Fowler Jr JF, et al. Patch testing in children from 2005 to 2012: results from the North American Contact Dermatitis Group. Dermatitis. 2014;25(6):345-55.

9. Cattani CAS, Oppermann K, Perazzoli S, Guarda NH, Barea P, Bonamigo RR. Sensitizing agents found in children and adolescents with recalcitrant atopic dermatitis: a cross-sectional study with a pediatric battery. An Bras Dermatol. 2022;97(3):307-14.

10. Mortz CG, Andersen KE. Allergic contact dermatitis in children and adolescents. Contact Dermatitis. 1999;41:121-30.

11. Boonstra M, Rustemeyer T, Middelkamp-Hup MA. Both children and adult patients with difficult-to-treat atopic dermatitis have high prevalences of concomitant allergic contact dermatitis and are frequently polysensitized. J Eur Acad Dermatol Venereol. 2018;32(9):1554-61.

12. Boonchai W, Chaiyabutr C, Charoenpipatsin N, Sukakul T. Pediatric contact allergy: A comparative study with adults. Contact Dermatitis. 2021;84(1):34-40.

13. Silverberg JI, Patel N, Warshaw EM, DeKoven JG, Atwater AR, Belsito DV, et al. Lanolin allergic reactions: North American

    
    

    Contact Dermatitis Group experience, 2001 to 2018. Dermatitis. 2022;33(3):193-99.

14. Jacob SE, Herro EM, Sullivan K, Matiz C, Eichenfield L, Hamann

    C. Safety and efficacy evaluation of TRUE TEST panels 1.1, 2.1, and 3.1 in children and adolescents. Dermatitis. 2011;22(4): 204-10.

15. Uldahl A, Engfeldt M, Svedman C. Clinical relevance of positive patch test reactions to lanolin: a ROAT study. Contact Dermatitis. 2021;84(1):41-9.

16. Jacob SE, Amini S. Cocamidopropyl betaine. Dermatitis. 2008;19(3):157-60.

17. Belloni Fortina A, Fontana E, Peserico A. Contact sensitization in children: a retrospective study of 2,614 children from a single center. Pediatr Dermatol. 2016;33(4):399-404.

18. Jacob SE, McGowan M, Silverberg NB, Pelletier JL, Fonacier L, Mousdicas N, et al. Pediatric contact dermatitis registry data on contact allergy in children with atopic dermatitis. JAMA Dermatol. 2017;153(8):765-70.

19. Mortazavi H, Ehsani A, Sajjadi SS, Aghazadeh N, Arian E. Patch testing in Iranian children with allergic contact dermatitis. BMC Dermatol. 2016;16(1):10.

Perceptions and Management Practices of Onychomycosis Among Thai Physicians

Pichaya Limphoka, M.D.*, Charussri Leeyaphan, M.D.*, Chudapa Sereeaphinan, M.D.*, Pattriya Chanyachailert, M.D.*, Sumanas Bunyaratavej, M.D.*, Carren Hau, M.D., Ph.D.**

*Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, **Section of Dermatology, Department of Internal Medicine, Manila Doctors Hospital, Manila, Philippines.

ABSTRACT

Objective: To examine the proportion of physicians who conducted mycological laboratory procedures to confirm a diagnosis of onychomycosis. The secondary purpose was to evaluate the practical management of physicians, comparing general practitioners and dermatology-related physicians.

Materials and Methods: This cross-sectional study and questionnaire-based research was conducted during 2021-2022. The questionnaire was composed of questions related to the practical management of onychomycosis, including diagnosis and treatment.

Results: Overall, 143 physicians were recruited to take part in this study. The number of physicians who conducted direct examination with potassium hydroxide was 99 (69.2%). The number of dermatology-related physicians who conducted mycological laboratory examinations to confirm the diagnosis was significantly higher than among general physicians (95.8% vs. 52.2%; p<0.001). Feet examination and determination of poor prognostic factors, such as elderly age, nail thickness, presence of dermatophytoma and nondermatophytes infection, were done by the dermatology-related physicians in significantly higher numbers. Blood testing before starting treatment for onychomycosis with oral antifungal medications seemed to be higher (87.5%) in the dermatology-related group. Moreover, mycological re-evaluation after treatment cessation was more significantly requested by the dermatology- related participants (75% vs. 15.8%, p<0.001).

Conclusion: Laboratory confirmation, feet examination, and the recognition of poor prognostic factors were significantly lower in the general practitioner group. These findings should raise awareness for improving further education about onychomycosis management in medical students, since mycological laboratory examination is crucial for diagnosis and it is helpful in guiding the proper disease management for complete disease remission.

Keywords: Mycological laboratory; general practitioners (Siriraj Med J 2023; 75: 76-84)

INTRODUCTION

Onychomycosis is one of the most common nail diseases worldwide.1 The prevalence of onychomycosis in the Asian population is approximately 10%.1 The diagnosis of onychomycosis requires both characteristic clinical manifestations and laboratory investigation.2 Clinical manifestations that are suggestive of onychomycosis are

subungual hyperkeratosis, onycholysis, nail discoloration, or nail dystrophy. However, there are a number of diseases, including chronic trauma, lichen planus, psoriasis, and subungual malignant melanoma, that mimic the features of onychomycosis.2,3,14 A previous study showed that about 65% of general practitioners misdiagnosed psoriatic nails as onychomycosis.4 Therefore, laboratory investigations,

Corresponding author: Sumanas Bunyaratavej E-mail: consultskin@yahoo.com

Received 24 May 2022 Revised 28 June 2022 Accepted 29 June 2022 ORCID ID:http://orcid.org/0000-0002-0852-7742 https://doi.org/10.33192/smj.v75i2.260741

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

involving either direct microscopic examination with potassium hydroxide or fungal culture, are essential to confirm the diagnosis of onychomycosis. Fungal culture is also beneficial in identifying the specific species of pathogen, and can help physicians to make the correct decision and to adjust the proper treatments to individual patients.2,5

The treatment of onychomycosis often requires long-term treatment.6 Oral antifungal treatments, such as allylamine terbinafine and the triazole group, have potential systemic side effects, such as hepatic involvement.7,8 Several studies have revealed an inappropriate management of onychomycosis among physicians.5 For example, a survey in the United Kingdom found that only a small proportion of physicians conducted laboratory confirmation before treating onychomycosis with oral terbinafine.7 One research study found that only 30% of dermatologists performed laboratory monitoring during oral terbinafine treatment.5

The objective of the present study was to determine the proportion of physicians who conducted mycological laboratory examination prior to a diagnosis of onychomycosis. We also aimed to evaluate the practical management of physicians, by comparing general practitioners with dermatology-related physicians.

MATERIALS AND METHODS

Study design

This cross-sectional study was a questionnaire-based research and was conducted during 2021-2022. This study was approved by the Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital (COA no. Si 733/2021). The questionnaire was developed and divided into four parts. The initial part aimed to collect the participants’ demographic data, including age, sex, marital status, workplace, working experience, and level of confidence in onychomycosis management. The other three parts were: 1) the opinions regarding the laboratory investigation request, covering 5 items; 2) the prognostic evaluation of onychomycosis, covering 10 items; and 3) the knowledge and practice for onychomycosis treatment, covering 6 items. Each variable item was recorded as categorical data. Google Forms was used as a channel to send the questionnaire. The study participants must be physicians who practice in Thailand.

Statistical analysis

Data were analyzed using PASW Statistics for Windows, version 18 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were presented as frequency and percentage. The Chi-square test or Fisher’s exact test

were used to compare the differences between the general practitioners and dermatology-related participants. A p-value less than 0.05 was considered as statistically significant.

RESULTS

In total, 143 physicians were recruited to participate in the study. Their demographic data are shown in Table 1. Their mean (SD) age was 33.9 (7.8) years old, while the minimum and maximum ages were 21 and 62 years old, respectively. Among the participants, 48 (33.6%) were dermatology-related physicians, comprising 23 (16.1%) who were board-certified dermatologists (16.1%) and 25 (17.5%) who were MSc, diploma, or in-training dermatology residents. Most participants worked in a university-based hospital. The minimum working experience was 1 year, while the maximum was 36 years. Most participants saw 0-5 patients per week (50%) and had low to moderate confidence in skin disease management. Regarding nail disease, 47 (32.9%) participants encountered patients with nail problems in 2-5 cases per year. The majority of participants (41.3%) reported that they had a moderate level of confidence in onychomycosis management.

Table 2 shows the information about onychomycosis diagnosis when comparing the dermatology-related physicians with general practitioners. The proportion of physicians who conducted direct examination with potassium hydroxide was 69.2%. The opinion that laboratory investigations were necessary for onychomycosis diagnosis was significantly higher in the dermatology-related physicians (97.9% vs. 54.7%, p < 0.001). In practical

management, 30 (62.5%) dermatology-related participants requested laboratory investigations almost or every time, which was significantly higher than for the other group (62.5% vs. 13.7%, p < 0.001). The presence of distinct clinical features of onychomycosis were the major cause for not requesting laboratory examinations. The significant reason those general practitioners did not request laboratory examinations to confirm diagnosis was the lack of knowledge of specimen processing (p < 0.001). Nail fungal culture was requested significantly more by the dermatology-related participants (79.2% vs. 37.9%, p < 0.001). The opinion that fungal culture was necessary was also significantly higher among dermatology-related physicians (89.6% vs. 50.5%, p < 0.001).

Table 3 demonstrates the prognostic evaluations of onychomycosis. Most participants had an awareness of poor prognosis factors, especially in the dermatologist- related group. An older age > 70 years old, nail thickness > 2 mm, presence of dermatophytoma and Neoscytalidium spp. infection were factors that the dermatology-related

TABLE 1. Demographic data of the participants.

Status

General practitioner

Specialist other than dermatologist

MSc, diploma, dermatology resident in training

Board-certified dermatologist

Other specialists

45 (31.5)

45 (31.5)

25 (17.5)

23 (16.1)

5 (3.5)

Demographic data

Total physicians

n = 143 (%)

Age, years (mean, SD) 33.9 (7.7)

Workplace*

University hospital 60 (42.0)

General hospital 35 (24.5)

Community hospital 16 (11.2)

Private hospital 31 (21.7)

Private clinic 28(19.6)

Working experience, years (mean, SD) 9.2 (6.9)

Number of skin patients during last one year (patients per week)

0–5 72 (50.3)

6–15 18 (12.6)

16–30 17 (11.9)

31–50 13 (9.1)

>50 23 (16.1)

*One physician could have more than one workplace.

Abbreviation: SD, standard deviation

TABLE 2. Comparison of the proportion between Thai general practitioners and dermatologic-related physicians regarding requesting laboratory investigations for onychomycosis diagnosis and treatment.

*A p-value less than 0.05 indicated statistical significance, Chi-squared test.

aOne physician could have more than one reason for not requesting laboratory investigations or one investigation that could be requested for the diagnosis and treatment of onychomycosis.

bSome participants responded to the questionaries in this topic.

TABLE 3. Prognostic evaluation of onychomycosis.

TABLE 3. Prognostic evaluation of onychomycosis. (Continued)

*A p-value less than 0.05 indicated statistical significance, Chi-squared test.

aOne physician could consider more than one factor to be a prognostic factor.

participants significantly had more awareness of (p < 0.001). Neoscytalidium spp. was significantly more well known in the dermatology-related group (87.5% vs. 26.3%, p < 0.001). Feet examination was significantly done every time by the dermatology-related participants (81.3%, p < 0.001). Among the general practitioners, nail thickness measurement and laboratory request after treatment were less frequently done (p < 0.001). Before starting treatment for onychomycosis with oral antifungal agents, blood testing seemed to be more frequently ordered in the dermatology-related group.

Treatment of the onychomycosis aspects are shown in Table 4. The use of topical therapy was significantly higher in the dermatology-related group (81.3% vs. 34.7%, p < 0.001). Also, 41.7% of the dermatology-related group participants used oral antifungal agents almost or every

time. Most participants did not agree with surgical nail avulsion as a treatment option. However, the indications for surgical nail avulsion were not recognized in the non-dermatology-related group (70.5%). Chemical nail avulsion was used significantly more by the dermatology- related participants (62.5% vs. 3.2%, p < 0.001).

DISCUSSION

The results provide interesting information about onychomycosis practice in Thailand. Most participants in this survey had encountered only a small number of patients suspected of onychomycosis. However, almost half of the participants had a moderate level of confidence in managing onychomycosis.

We found that nearly all the dermatology-related physicians used laboratory investigations to confirm

TABLE 4. Knowledge and practice for onychomycosis treatment.

*A p-value less than 0.05 indicated statistical significance, Chi-squared test.

the diagnosis, which was consistent with the result of a study in Canada.9 Unfortunately, almost half of the general practitioners never used mycological laboratory examinations to confirm the diagnosis of onychomycosis. These results were similar to several studies that reported that general practitioners tended to treat onychomycosis without the mycological evidence of fungal infection5,6 This study showed that the most common reason for not performing mycological laboratory examinations was the belief that the clinical manifestations were sufficient for diagnosis. Nevertheless, the lack of knowledge in specimen processing was found to be significantly different between the two groups. More than half of the participants conducted fungal culture. However, the proportion who conducted fungal culture was significantly higher among the dermatology-related physicians. This emphasized that knowledge played a key role in onychomycosis management. In addition, this study revealed that the second most-common reason for general practitioners not to perform mycological investigations was the lack of accessibility to laboratory facilities. Therefore, easily accessible mycological laboratory facilities may motivate physicians to use mycological investigations to confirm the diagnosis. Several studies also demonstrated other reasons, such as general practitioners had insufficient skills or it was time-consuming to collect specimens, or they felt familiar through previous individual practice.5,9 Cases of concurrent onychomycosis and tinea pedis were also reported.10 Our study revealed that a significantly lower number of general practitioners did feet examination compared to the dermatology-related physicians. Examination of the feet was recommended in patients diagnosed with onychomycosis, since tinea pedis could be reservoirs of infection, resulting in unsuccessful treatment.10 Poor prognostic factors, including elderly age, longer onset, presence of cardiovascular diseases, widespread dermatophyte infection, and multiple nail infection, were found to be associated with a poorer outcome.11,12 In this study, the poor prognostic factors that were significantly underrecognized by the general practitioners were an elderly age, subungual hyperkeratosis (>2 mm), presence of dermatophytoma, and NDM infection. Greater education for general practitioners to recognize the prognostic factors would result in a better

treatment outcome.12

According to the results from this study, oral antifungal drugs were often used by dermatology-related physicians more than by general practitioners. This study showed the same percentage of general practitioners who never used oral antifungal drugs as a treatment option.7 Almost half of the physicians performed blood tests before

starting oral antifungal agents, but the proportion was not statistically significant between the two groups. Oral terbinafine is an effective drug in treating dermatophyte onychomycosis. However, terbinafine is expensive and can cause adverse side effects, such as hepatic involvement (elevated hepatic enzymes).5 It is thus recommended that oral antifungal agents should be prescribed only when physicians see characteristic clinical manifestations and when mycological laboratory examinations confirm the diagnosis of onychomycosis.5,7 Our study showed that the percentage of general practitioners who never conducted blood testing prior to prescribing oral antifungal agents was 27.4%. This proportion was lower compared to a previous study that showed 36% of general practitioners had never done a blood test.7 Blood testing for complete blood count and liver function prior to starting oral antifungals was suggested by some experts.6 Monitoring the laboratory results during treatment with oral antifungal drugs is still controversial. Unsurprisingly, in one study it was found that the percentage of dermatologists who monitored blood tests during using oral antifungal therapy was only 30%.9 Some authors suggested that the careful monitoring of blood testing is recommended in patients with underlying hepatic disease.6

The opinion regarding performing follow-up laboratory examination after the cessation of treatment was significantly higher in the dermatology-related group. When practicing, almost all the general practitioners never performed laboratory investigations after the completion of treatment. The reasons for this were that they may perform mycological investigations only in cases with no response or in suboptimal treatment or recurrent disease cases.6,7

A 43-year retrospective study of lawsuits involving nail conditions in the United States found that the most common reason was inadequate treatment causing undesirable sequalae, which was found in 19 cases (51%).13 Unfortunately, misdiagnosis leading to a serious issue was the major reason why lawsuits were won by the plaintiff.13

In conclusion, the laboratory confirmation of onychomycosis was significantly lower in the general practitioner group. However, in all cases of suspected onychomycosis, mycological laboratory examinations to confirm the diagnosis are crucial.6,7,14 A clear guideline for onychomycosis management and concrete evidence supporting mycological laboratory examinations as essential for onychomycosis diagnosis may be helpful to guide the proper management.7 Laboratory investigations prior and during the administration of oral antifungal drugs are still inconclusive. Further studies about the benefits and cost

effectiveness are needed. Easily accessible mycological laboratory facilities will also motivate physicians to conduct proper investigations. This study also emphasizes that education is important for all physicians in order to ensure they can provide the proper management of onychomycosis, reduce adverse events, and provide the best care for patients.

Conflict of interests: All authors have no conflicts of interest or financial support to declare.

Funding: None

REFERENCES

1. Sigurgeirsson B, Baran R. The prevalence of onychomycosis in the global population: a literature study. J Eur Acad Dermatol Venereol. 2014;28(11):1480-91.

2. Ameen M, Lear JT, Madan V, Mohd Mustapa MF, Richardson M. British Association of Dermatologists’ guidelines for the management of onychomycosis 2014. Br J Dermatol. 2014; 171(5):937-58.

3. Denning DW, Evans EG, Kibbler CC, Richardson MD, Roberts MM, Rogers TR, et al. Fungal nail disease: a guide to good practice (report of a Working Group of the British Society for Medical Mycology). BMJ. 1995;311(7015):1277-81.

4. Bunyaratavej S, Prasertworonun N, Chaiwanon O, Pattanaprichakul

   P. Alarming trend towards deviation of clinical diagnosis and management of psoriatic nails by Thai general practitioners and non-dermatologist specialists. J Eur Acad Dermatol Venereol.

   2015;29(2):398-9.

5. Wilcock M, Hartley J, Gould D. Inappropriate use of oral terbinafine in family practice. Pharm World Sci. 2003;25(1): 25-6.

6. Gupta AK, Mays RR, Versteeg SG, Piraccini BM, Takwale A, Shemer A, et al. Global perspectives for the management of onychomycosis. Int J Dermatol. 2019;58(10):1118-29.

7. Lasseter G, McNulty CA, Palmer M, Yoxall H, Kibbler C, Health Protection Agency GPMLUG. Developing best practice for fungal specimen submission--fungal audit of general practice. Mycoses. 2012;55(6):476-82.

8. Wharry S. FDA issues warnings about drugs used to treat fungal nail infections. CMAJ. 2001;164(12):1738.

9. Gupta AK, Shear NH. A questionnaire study on the management of onychomycosis: a Canadian perspective. Int J Dermatol. 1998;37(6):457-60.

10. Walling HW. Subclinical onychomycosis is associated with tinea pedis. Br J Dermatol. 2009;161(4):746-9.

11. Loo DS. Onychomycosis in the elderly: drug treatment options. Drugs Aging. 2007;24(4):293-302.

12. Widaty S, Miranda E, Bramono K, Menaldi SL, Marissa M, Oktarina C, et al. Prognostic factors influencing the treatment outcome of onychomycosis Candida. Mycoses. 2020;63(1):71-7.

13. Xiang L, Lipner SR. Characteristics of malpractice lawsuits involving nail disorders in the United States from 1977 to 2019. J Am Acad Dermatol. 2020;83(4):1202-4.

14. Leeyaphan C, Bunyaratavej S, Chadchavalpanichaya N, Rujitharanawong C, Phaitoonwattanakij S, Matthapan L. Clinical and Laboratory Findings in Trauma-Induced Nail Dystrophy versus Onychomycosis. Siriraj Med J. 2018;70(6): 490-5.

Clinical Features of Adult Male Acne in a Tropical Country: A Prospective Cross-sectional Study

Chayanee Likitwattananurak, M.D., Leena Chularojanamontri, M.D., Papapit Tuchinda, M.D., Kanokvalai Kulthanan, M.D.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: To evaluate the characteristics of post-adolescent male patients with acne in terms of the onset of the condition, its clinical course and severity, and the behaviors associated with its severity.

Materials and Methods: A prospective, cross-sectional study was conducted on adult males with acne who visited Siriraj Hospital, Thailand. All male acne patients aged 21 years and older were enrolled. Diagnoses and physical examinations were performed by dermatologists.

Results: Seventy-two patients (mean age, 26.9 [± 4.3] years) were included. Persistent acne, relapse acne, and late- onset acne (onset at age ≥ 21 years) were reported in 62.5%, 33.3%, and 4.2% cases, respectively. Persistent acne tended to subside at 26 years of age, whereas late-onset acne tended to start at 28 years of age. The acne severity was mild in most cases. Pimple-picking, followed by frequent face washing, were common habits among male acne patients. Shaving influenced the severity in some adult male with acne.

Conclusion: Adult male acne commonly presented as inflammatory lesions and comedones on the cheeks. They commonly had an onset earlier than 21 years old and continued into adulthood, but the post-adolescent severity tended to be mild. While several factors have been reported elsewhere to be involved in the severity of acne, this study found that only shaving influenced severity.

Keywords: Acne vulgaris; adult acne; male (Siriraj Med J 2023; 75: 85-91)

INTRODUCTION

Acne vulgaris is chronic inflammatory skin disease characterized by open and closed comedones, inflammatory papules, pustules, and nodules in seborrheic areas.1,2 It is one of the most troublesome skin diseases. The pathogenesis of acne involves the colonization and proliferation of Corynebacterium acnes, resulting in the inflammatory process, hyperkeratinization, and sebum hyperproduction.2,3 The negative effects of acne vulgaris include depression, antisocial behavior, and even unemployment. The prevalence of acne vulgaris is 90%-95% of the population.3,4 Acne commonly occurs

during adolescence, and it is found less often during the pre- and post-adolescent periods.3

Adolescent acne predominantly occurs in males, while post-adolescent acne is usually found in females.5 However, post-adolescent acne or adult acne can also affect male patients. Adult patients with acne have many challenging problems. For instance, the acne may develop therapeutic resistance or respond slowly to treatment; the skin can also easily become allergic to topical treatments, leading to drug discontinuation. Previous studies have identified a wide variety of factors related to acne severity in adolescent acne rather than post-adolescent acne.3-5

Corresponding author: Kanokvalai Kulthanan E-mail: kanokvalai.kul@mahidol.ac.th

Received 18 March 2022 Revised 7 July 2022 Accepted 9 July 2022 ORCID ID:http://orcid.org/0000-0002-7618-821X https://doi.org/10.33192/smj.v75i2.260742

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

Based on our literature review, data from prospective studies focusing on post-adolescent male patients with acne is limited. The present study aimed to evaluate the characteristics of post-adolescent male patients with acne in terms of its onset, clinical course, and severity, and the behaviors associated with the severity of acne.

MATERIAL AND METHODS

This study was ethically approved by the Institutional Review Board SIRB 796/2018 (EC4), COA no Si 018/2019. Adult male patients were recruited if they had acne, were aged 21 years or older,6 and attended the Outpatient Dermatologic Clinic, Siriraj Hospital, between January 2019 and June 2020. Informed consent was obtained from all of the patients. The demographic data collected included the patients’ present ages, their age at acne onset, and aggravating factors. The acne was classified into 3 types: persistent, late-onset, and relapse. Persistent acne was defined as acne that had an onset earlier than 21 years of age and which continued into adult life. Late-onset acne was defined as acne with an onset of

≥ 21 years of age (usually between 21 and 25 years of age). Relapse acne referred to acne that had an onset earlier than 21 years of age, but subsequently subsided before recurring sometime after remission.6

A record was made of each patient’s skin type (oily; normal; dry; and mixed [oily nose, and normal- to-dry skin on the cheeks]), which was determined by a combination of history taking and physical examination. All of the physical examinations were conducted by the one dermatologist (CL). Severity of acne was recorded throughout all affected areas such as the whole face, neck, chest and back. The severity of the acne, and its location and characteristics were characterized using the Investigator’s Global Assessment (IGA) severity scale. IGA offers a composite score to define acne severity, and the tool has been accepted by the U.S. Food and Drug Administration. The acne severity can be assessed using two methods. With the first method, the acne severity is classed as “mild”, “moderate”, or “severe”, depending on the number of comedones, inflammatory lesions, lesions, and pseudocysts. Mild acne has < 20 comedones, < 15 inflammatory papules, a total lesion count of < 30, and no pseudocysts. Moderate acne has 20–100 comedones, 15–50 inflammatory lesions, a total lesion count of 30–125, and no pseudocysts. Severe acne has > 100 comedones, > 50 inflammatory lesions, a total lesion count of > 125, and > 5 pseudocysts. The second classification method utilizes a five-point scale: 0 = “clear”, 1 = “almost clear”, 2 = “mild”, 3 = “moderate”, and 4 = “severe”. Clear acne means that there are no lesions,

while almost-clear acne describes the condition in which there are rare noninflammatory lesions and only one inflammatory lesion. Mild acne has some noninflammatory lesions and 2–3 inflammatory lesions. Moderate acne has many noninflammatory lesions, some inflammatory lesions, and one nodular lesion. Severe acne has many noninflammatory and inflammatory lesions, as well as 2–3 nodular lesions.7

An evaluation was made of the patients’ acne complications, such as post-inflammatory hypo/ hyperpigmentation, pitted (atrophic) scarring, and hypertrophic scarring. Additionally, the Global Scale for Acne Scar Severity (SCAR-S) system was used to categorize the severity of scars as “macular”, “mild”, “moderate”, and “severe”. A macular scar is defined as an erythematous, post-inflammatory hypo/hyperpigmentation scar without any textural change. A mild scar presents a mild atrophic appearance, and the scar can be covered by makeup or facial hair. A moderate scar can be covered by manually stretching the skin, but not by makeup. A severe scar is a permanent scar that cannot be removed by stretching the skin.8

Data were analyzed using PASW Statistics for Windows (version 18.0; SPSS Inc., Chicago, Ill., USA). P-values less than 0.05 indicates statistical significance.

RESULTS

Seventy-two male patients with acne were enrolled. Their mean age was 26.9 ± 4.3 years, and their mean body mass index was 21.9 ± 3.0 kilogram/m2. The mean age of acne onset was 15.3 ± 2.5 years. Onset of the patients’ secondary sex characteristics occurred between 12 and 18 years of age, with the mean age of onset of voice cracks, shin-hair growth, and beard growth being 14.4 ± 1.6,

15.1 ± 2.3, and 15.6 ± 2.1 years, respectively. Seventy-two percent had a positive family history of acne; of those, 94.2% had first-degree relatives with acne while the rest (5.8%) had second-degree relatives with acne. Table 1 details the skin and acne types, acne severities, habits related to acne, and previous treatments. Over half of the patients (55.6%) had the oily skin type, while 37.5% had the mixed type. Most cases were of the persistent acne type, followed by relapse acne and then late-onset acne. With the persistent acne group, the condition first developed at the mean age of 15.1 ± 1.9 years, continued to 26.4 ± 5.7 years of age, and then subsided. As to the relapse group, the acne first appeared at the mean age of

15.4 ± 1.9 years; it subsequently subsided for a duration of 9.7 ± 8.2 years before recurring at the age of 24.3 ± 4.4 years. The late-onset acne commenced at 27.7 ± 2.5 years of age.

TABLE 1. Demographic data and previous treatments of adult male acne patients.

Characteristics N/72 (%)

Previous treatment

Topical medications

Abbreviation: IGA, Investigator’s Global Assessment

According to the IGA-scale severity assessments, the majority of our patients had mild acne. Pimple picking, followed by frequent facial washing, were common habits during the acne period of the male patients. The advice of dermatologists was sought by 45.8% of the 72 patients, and a comparable proportion (43.0%) consulted general practitioners. A sizeable minority (19.4%) bought over-the-counter medications, but very few patients

(1.4%) sought treatment at beauty salons. Most used several therapies for their acne. The most common topical treatment was benzoyl peroxide in conjunction with topical antibiotics. Doxycycline was the most frequently used antibiotic; the 2 antibiotics, sulfamethoxazole and trimethoprim, were used in combination by a minority of patients.

The most common locations on the face were the

cheeks (100%), the chin (68.1%), and the forehead (54.7%). The most frequently observed clinical presentation was inflammatory lesions, followed by whitehead comedones, blackhead comedones, and nodular lesions. Our study revealed the types of acne lesions that were present at various locations of the face. (Fig 1) Inflammatory acne was usually found around the cheeks and perioral areas, whereas whitehead comedones typically occurred on the forehead. One-third of the patients had acne on both facial and non facial areas (such as the chest and back). Post-inflammatory hypo/hyperpigmentation (75%)

and pitted (atrophic) scarring (72.2%) were common complications, but hypertrophic scarring was found in only 12.5% of the cohort. Based on the SCAR-S system, 40.3%, 29.2%, 29.2%, and 1.3% had macular, mild, moderate, and severe scarring, respectively. One patient with severe scarring had a history of anabolic steroid use for body building during the acne period. Table 2 lists the factors that were deemed to be potentially associated with acne severity. The proportion of patients who frequently shaved their beard was significantly higher for patients with moderate-to-severe acne than patients with mild acne. However, it should be noted that of the 29 patients who frequently shaved their beard, 20 (69%) had acne lesions on the chin.

DISCUSSION

Acne is a chronic inflammatory skin disease affecting all generations of the population. The results of our study are consistent with those of previous studies on females in that persistent acne was found to be the most common type of post-adolescent acne.6 However, the common acne locations in our male patients (the forehead and both cheeks) differed from those reported for post-adolescent females (the lower face: chin, jawline, and neck).9,10 The data on the predominant type of lesions found in female acne are controversial. A review by Holzmann et al. showed that comedones were usually minimal or absent, yet Bagatin et al. reported that comedones were the most common type. Our study showed that inflammatory papules and comedones were common types of acne in post-adolescent male patients, which is similar to the adolescent-acne patterns found for both genders.6,9-10

Regarding acne complications, an Indian study by Khunger et al. claimed that post-acne scarring is more frequent in adults than adolescents due to treatment resistance and delayed therapy.14 It has also been reported elsewhere that adult male patients tend to have more acne scarring than adult female patients.3 The acne complications found by Khunger and colleagues were-in descending order of frequency-pigmentary changes, icepicks, rolling,

Fig 1. Clinical presentation of adult male acne on different locations of the face.

Abbreviations: B, blackheads: C, closed comedones: I, inflammatory papules: N, nodular lesions

TABLE 2. Factors associated with the severity of male acne in this study.

Remark: a p-value less than 0.05 indicates statistical significance.

atrophic scarring, and keloidal scarring; this sequence is consistent with the findings of our study.14 One Polish population-based observational study conducted by Chlebus et al. found that 53.9% of the adult patients with persistent acne had scarring.15 Our study revealed a higher prevalence of scarring than that reported by Chlebus and colleagues. Rawling et al. reviewed that the Asian skin type has a thinner stratum corneum which is the epidermal outermost layer and protective layer, resulting in more skin barrier defects.16 This may explain that the Asian skin type is more vulnerable to forming scar tissue than Caucasian skin. Thus, Asian skin may require different care methods.

Table 3 summarizes the factors identified by previous studies as being associated with acne severity in post- adolescent male and female patients. The likelihood of having the more severe forms of acne was reported to increase with family history of acne; the consumption of high-dairy, fatty, or sugary diets; the drinking of milk and sugary beverages; the presence of hirsutism, acanthosis

nigricans, or excessive seborrhea; chemical substance exposure; smoking; acne onset during adolescence; and the male gender.1,5,9,11-12,15,18,21,23-25 Smoking has been shown to be able to increase and decrease acne severity, especially in male patients.1,13,16,19 Due to the limited number of patients, our study did not find any significant differences between the mild and moderate-to-severe acne groups in terms of the aforementioned factors. However, shaving was significantly found more often in patients with the more severe forms of acne. We assumed that the shaving technique employed and the use, or non-use, of a shaving gel or cream might contribute to this finding. It should be noted that our study and the work by Klaz and colleague comprised only male patients.17

There are some limitations to our study. Firstly, a limited number of patients were enrolled. Moreover, this work was conducted at a tertiary hospital in Thailand, and not on the general population; the results may therefore not be generalizable. Lastly, this research did not include male-to-female transgender individuals, who may receive

Likitwattananurak et al.

TABLE 3. Comparison of previous studies on post-adolescent acne with our study.

Abbreviations: BMI, body mass index (kg/m2); EU, European; N/A, not applicable; yrs, years

90 Volume 75, No.2: 2023 Siriraj Medical Journal https://he02.tci-thaijo.org/index.php/sirirajmedj/index

estrogens and/or antiandrogens. Thus, our findings may not be applicable to this group of patients.

To summarize, in our tropical country, the male patients with post-adolescent acne usually presented with inflammatory lesions and comedones, which were predominantly located on the cheeks. They commonly had an onset earlier than 21 years of age and continued into adulthood, but the severity during the post-adolescent period tended to be mild. While several factors have been reported elsewhere to be involved in the severity of acne, this study found that only shaving influenced severity.

ACKNOWLEDGEMENT

The authors gratefully acknowledge Ms. Saowalak Hunnangkul for her assistance with the statistical analyses. This was an unfunded study.

Conflict of interest: The authors declare that there are no personal or professional conflicts of interest regarding any aspect of this study.

REFERENCES

1. Heng AHS, Chew FT. Systematic review of the epidemiology of acne vulgaris. Sci Rep. 2020;10:5754.

2. Thiboutot DM, Dréno B, Abanmi A, Alexis AF, Araviiskaia E, Barona Cabal MI, et al. Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcome in Acne. J Am Acad Dermatol. 2018;78:S1- S23.e1.

3. Skroza N, Tolino E, Mambrin A, Zuber S, Balduzzi V, Marchesiello A, et al. Adult acne versus adolescent acne: a retrospective study of 1,167 patients. J Clin Aesthet Dermatol. 2018;11:21-5.

4. Chlebus E, Chlebus M. Factor affecting the course and severity of adult acne: Observational cohort study. J Dermatolog Treat. 2017;28:737-44.

5. Penso L, Touvier M, Deschasaux M, Szabo de Edelenyi F, Hercberg S, Ezzedine K, et al. Association between adult acne and dietary behaviors findings from the Nutrinet-Sante’ Prospective cohort study. JAMA Dermatol. 2020;156:854-62.

6. Holzmann R, Shakery K. Postadolescent acne in females. Skin Pharmacol Physiol. 2014; 27 Suppl 1:3-8.

7. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Acne Vulgaris: establishing effectiveness of drugs intended for treatment guidance for industry [Internet]. 2018 [cited 2021 Jan 21]. Available from: https://www.fda.gov/regulatory- information/search-fda-guidance-documents/acne-vulgaris- establishing-effectiveness-drugs-intended-treatment.

8. Clark AK, Saric S, Sivamani RK. Acne Scars: How Do We Grade Them? Am J Clin Dermatol. 2018;19:139-44.

9. Kaminsky A, Florez-White M, Bagatin E, Arias MI. Large prospective study on adult acne in Latin America and the Iberian Peninsula: risk factors, demographics, and clinical characteristics. Int J Dermatol. 2019;58:1277-82.

10. Bagatin E, Freitas THP, Rivitti-Machado MC, Machado MCR, Ribeiro BM, Nunes S, et al. Adult female acne: a guide to clinical practice. An Bras Dermatol. 2019;94:62-75.

11. Goulden V, McGeown H, Cunliffe WJ. The familial risk of adult acne: comparison between first-degree relatives of affected and unaffected individuals. Br J Dermatol. 1999;141:297-300.

12. Ismail NH, Manaf ZA, Azizan NZ. High glycemic load diet, milk and ice cream consumption are related to acne vulgaris in Malaysian young adults: a case control study. BMC Dermatol. 2012;12:13.

13. Schäfer T, Nienhaus A, Vieluf D, Berger J, Ring J. Epidemiology of acne in the general population: the risk of smoking. Br J Dermatol. 2001;145:100-4.

14. Khunger N, Kumar C. A clinico-epidemiological study of adult acne: is it different from adolescent acne? Indian J Dermatol Venereol Leprol. 2012;78:335-41.

15. Chlebus E, Chlebus M. The role of adolescent acne treatment in formation of scars Among patients with persistent adult acne: evidence from an observational study. Cutis. 2019;104: 57-61.

16. Rawlings AV. Ethnic skin types: are there differences in skin structure and function? Int J Cosmet Sci. 2006;28:79-93.

17. Klaz I, Kochba I, Shohat T, Zarka S, Brenner S. Severe acne vulgaris and tobacco smoking in young men. J Invest Dermatol. 2006;126:1749-52.

18. Wei B, Pang Y, Zhu H, Qu L, Xiao T, Wei HC, et al. The epidemiology of adolescent acne in North East China. J Eur Acad Dermatol Venereol. 2010;24:953-7.

19. Karadağ AS, Balta I, Saricaoğlu H, Kiliç S, Kelekçi KH, Yildirim M, et al. The effect of personal, familial, and environmental characteristics on acne vulgaris: a prospective, multicenter, case controlled study. G Ital Dermatol Venereol. 2019;154:177- 85.

20. Xu SX, Wang HL, Fan X, Sun LD, Yang S, Wang PG, et al. The familial risk of acne vulgaris in Chinese Han—a case-control study. J Eur Acad Dermatol Venereol. 2007;21:602-5.

21. Wolkenstein P, Misery L, Amici JM, Maghia R, Branchoux S, Cazeau C, et al. Smoking and dietary factors associated with moderate-to-severe acne in French adolescents and young adults: results of a survey using a representative sample. Dermatology. 2015;230:34-9.

22. Di Landro A, Cazzaniga S, Parazzini F, Ingordo V, Cusano F, Atzori L, et al. Family history, body mass index, selected dietary factors, menstrual history, and risk of moderate to severe acne in adolescents and young adults. J Am Acad Dermatol. 2012; 67:1129-35.

23. Aalemi AK, Anwar I, Chen H. Dairy consumption and acne: a case control study in Kabul, Afghanistan. Clin Cosmet Investig Dermatol. 2019;12:481-7.

24. Wolkenstein P, Machovcová A, Szepietowski JC, Tennstedt D, Veraldi S, Delarue A. Acne prevalence and associations with lifestyle: a cross-sectional online survey of adolescents/young adults in 7 European countries. J Eur Acad Dermatol Venereol. 2018;32:298-306.

25. Ibrahim AA, Salem RM, El-Shimi OS, Baghdady SMA, Hussein

S. IL1A (-889) gene polymorphism is associated with the effect of diet as a risk factor in acne vulgaris. J Cosmet Dermatol. 2019;18:333-6.

Human-pet Relationship, Pet Abandonment, and Clinical Correlation for Patients Infected with Dermatophytosis of the Glabrous Skin

Sanchai Sombatmaithai, M.D.*, Sumanas Bunyaratavej, M.D.**, Pattriya Chanyachailert, M.D.**, Pichaya Limphoka, M.D.**, Chuda Rujitharanawong, M.D.**, Suthasanee Prasertsook, M.D.**, Charussri Leeyaphan, M.D.**, Carren S Hau, M.D., Ph.D.***

*Department of Dermatology, Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand, **Department of Dermatology, Faculty

of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, ***Section of Dermatology, Department of Internal Medicine, Manila Doctors Hospital, Manila, Philippines.

ABSTRACT

Objective: The study on human-pet relationship and pet abandonment among dermatophytosis patients is limited. This study aims to review these correlations.

Materials and Methods: A two-year retrospective cross-sectional study was conducted. Case record forms were reviewed for clinical manifestations, fungal identification, human-pet relationships, and changes in the relationships after dermatophytosis diagnosis.

Results: A total of 230 dermatophytosis patients from the Dermatology outpatient clinic, Siriraj Hospital, were included. The mean age was 41.9 ± 19.1 years and 51.3% were female. Among 170 cases with positive fungal culture, zoophilic dermatophytosis from M. canis infection was identified in 15.9% which was predominately found in females and manifested as shorter duration of onset, and higher involvement on exposed areas when compared to anthropophilic dermatophytosis. Most (71%) of patients with M. canis infection classified themselves as pet-lovers. The relationship with pets had changed after the dermatophytosis diagnosis in 41% of them which was statistically different from 8.8% in non-pet lovers (P = 0.001). The overall pet abandonment rate was 26.6%. The abandonment rate was 40.9% among non-pet lovers, while 30.6% was reported among pet lovers.

Conclusion: Zoophilic M. canis infection was associated with rapid onset and on predominant-exposed areas. Some pets could be asymptomatic, so identification of the reservoirs of dermatophytosis is important in the treatment process and helps prevent future recurrence. Paying attention to human-pet relationships and pet abandonment is critical. Knowledge about dermatophytosis transmission, and appropriate pet management should be advised to decrease abandonment.

Keywords: Dermatophyte; animals; Trichophyton; Microsporum; pet (Siriraj Med J 2023; 75: 92-98)

INTRODUCTION

Dermatophytosis is a common skin disease affecting humans. Depending on their reservoirs, the causative pathogens are classified into 3 groups: anthropophilic,

zoophilic, and geophilic dermatophytes.1 The anthropophilic dermatophytes are comprised of Trichophyton rubrum, Epidermophyton floccosum, Trichophyton violaceum, Trichophyton tonsurans, Trichophyton mentagrophytes var.

Corresponding author: Sumanas Bunyaratavej E-mail: consultskin@yahoo.com

Received 25 April 2022 Revised 18 June 2022 Accepted 20 June 2022 ORCID ID: https://orcid.org/0000-0002-0852-7742 http://dx.doi.org/10.33192/smj.v75i2.260745

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

interdigitale etc. The zoophilic dermatophytes consisted of Microsporum canis, Trichophyton mentagrophytes var. mentagrophytes (T. mentagrophytes), Trichophyton verrucosum etc.2 Zoophilic dermatophytes are transmitted to humans from animals, which are major reservoirs. These forms of dermatophytosis tend to cause inflammatory infections and atypical skin lesions in humans.3,4 The causative organisms vary geographically. M. canis and

T. verrucosum are the most common causative pathogens of zoophilic dermatophytosis in Southern European and Arabic countries.5,6 Moreover, the incidence of superficial skin infections with M. canis has significantly increased, suggesting that zoophilic dermatophytosis will eventually become a major health problem.5-8 Animal specificity has been reported for the zoophilic species of dermatophytes. Cats and dogs, for example, are the main reservoirs of

M. canis, which is common in Thailand. In tropical countries, people usually wear short sleeves and pants, which may increase the area exposed to infection. Contact between humans and animals is the chief influence in cases of zoophilic dermatophytosis.9,10 The animal-borne diseases could result in owners abandoning their pets.

The primary objective of this study was to investigate the human-pet relationship and pet abandonment in terms of the former emotional bonds and the psychological consequences after a diagnosis of a fungal infection. In addition, the clinical manifestations of dermatophytosis caused by zoophilic pathogens were also compared with anthropophilic dermatophytes.

MATERIALS AND METHODS

Study design

The study protocol was approved by the Siriraj Institutional Review Board (COA no. Si 564/2017). This was a 2-year, retrospective cross-sectional chart review. All data were recruited from the case record form of the outpatient fungal infection clinic, Department of Dermatology Siriraj Hospital, a tertiary hospital in Thailand, as every patient who visited our clinic was normally asked the questions via face-to-face interviews and then recorded in the case record form. Those patients diagnosed with dermatophytosis were included in this study. The diagnosis had been confirmed by clinical manifestation and mycological laboratory investigations, including potassium hydroxide preparation and/or fungal culture of dermatophytosis. All specimens were obtained from suspected glabrous skin lesions.

The clinical manifestation and history of having pets were reviewed. The relationship between the owners and their pets was described in 4 aspects, including the affection of the owners for their pets before the dermatophytosis

diagnosis, the area where the owners let their pets live in the house, the frequency of animal contact, and physical interaction with their pets. The emotional affection for the pets was graded subjectively by the owners as no, minimal, moderate, high, and extreme affection. Those who labeled themselves to have no or minimal affection for pets were grouped as “non-pet lovers”, and those labeled to have moderate, high, and extreme affection were “pet-lovers”. The areas where the pets live were classified as the bedroom, outdoor, indoor (any other areas out of the bedroom), and a cage. The frequency of animal contact was graded by the owners as never, sometimes, almost every day, and every day. The physical interaction with the pets was categorized as touch, and hug or kiss.

Their relationship with pets changed after the dermatophytosis diagnosis and the management of the pets after the skin infection diagnosis were also routinely recorded in the case record form of our clinic. Pet abandonment was divided into 2 groups: “no abandonment”, when the owners showered their pets more frequently and/or took their pets to visit vets, and “abandonment”, when the owners never made physical contact with their pets again.

Statistical analysis

Chi-squared and Fisher’s exact tests were used to compare the sites of skin lesions and the relationships between the animals and the owners. Logistic regression was used to analyze the factors associated with dermatophytosis. The statistical analyses were performed with the program IBM SPSS Statistics for Windows, version 18 (IBM Corp., Armonk, N.Y., USA). A significance P value of 0.05 was used.

RESULTS

Two hundred and thirty patients were included in this study. The mean age was 41.9 ± 19.1 years, with approximately half of the patients being female (51.3%). Among 130 current pet owners, the most common type of pets reported was dogs-only (46.9%), followed by cats- only (19.2%), and both dogs and cats (13.9%). Based on the 170 confirmed fungal cultures, 27 (15.9%) patients were definitely diagnosed with zoophilic dermatophytosis from M. canis infection, whereas 143 patients (84.1%) were reported as anthropophilic dermatophytosis. Comparisons of the demographic and clinical data were presented in Table 1. Females (88.9%) accounted for a significantly higher proportion of zoophilic infections from M. canis than males (11.1%; P = 0.006). In the case of zoophilic infections, the median duration from

TABLE 1. Factors associated with anthropophilic and zoophilic M. canis infections.

“Unexposed areas” of glabrous skin is defined as the trunk, upper arms, and upper legs; “exposed areas” of glabrous skin is defined as the face, neck, forearms, and lower legs; “undetermined areas” is defined as non-glabrous skin or thickened and hard keratin, including the palms, soles, hair, and scalp.

Fig 1. Tinea cruris, presenting with well-defined scaly erythematous annular plaques with hyperpigmentation on non-exposed areas. Anthropophilic dermatophyte T. rubrum was identified.

the onset of symptoms to the hospital-visit date was 10 days IQR (7, 14) which was statistically shorter than that for anthropophilic infections (median 90 days, IQR 30, 365, P < 0.001). Zoophilic dermatophytes were found at exposed areas (80%) of the body more than anthropophilic dermatophytes (33%; P = 0.008).

Fig 2. Tinea faciei from animal-transmitted infection, presenting with multiple, discrete, well-defined, erythematous annular plaques with excoriation on exposed areas. Zoophilic dermatophyte M. canis from her cat was the causative organism.

The pet and owner relationships were compared between anthropophilic and zoophilic infection, as shown in Table 2. The results demonstrated that the closer their relationship was, defining as the display of most/extreme affection, a high frequency of contact, and behavior of hugging or kissing their own pets, the higher the owners

TABLE 2. Relationship between the pet and patient associated with dermatophyte infections.

NA = not available.

took a zoophilic infection risk. The causative organisms were categorized and compared by the patients’ gender. As a result, T. rubrum, T. mentagrophytes complex, and

M. canis were the three most common dermatophytes found (53.4%, 26.1% and 11.7%, respectively). More female patients were infected with the zoophilic

M. canis than males (P < 0.001) whereas the anthropophilic

T. rubrum was mostly found in males (P < 0.001).

There were 161 patients with documented data regarding pets. Seventy-six patients (47.2%) did not have pets. The number of patients who had pets in the zoophilic dermatophytosis disease group (92.3%) was significantly higher than those with anthropophilic dermatophytosis (45.2%; P = 0.005). Dermatophyte species isolated from the owners of many kinds of pets were demonstrated in Table 3. It was also found that 61.9% of the patients infected with M. canis reported that their pets got hair loss or skin inflammation.

After the diagnosis of dermatophytosis, the overall patients reported showering their pets more frequently was 60.7%, took their pets to visit the vet 16.1%, and never

made physical contact with their pets again 23.2%. Sixty- one patients were classified as pet-lovers who reported their status change with pets. Twenty-five of them (41.0%) reported that the relationship with pets changed after the dermatophytosis diagnosis which was statistically different from 8.8% in non-pet lovers (P = 0.001), as shown in Table 3. One of the factors which contributed to these significant changes in the relationship might be due to the management of pets after the diagnosis. The patients who classified themselves as pet lovers took their pets to visit the vet more than those non-pet lovers. As a result, non-pet lovers demonstrated a 40.9% abandonment rate while the abandonment rate of pet-lovers was only 30.6% (P = 0.421). Overall recurrence rate was 24.7%, and pet-lovers (17.5%) had a significantly lower rate than non-pet lovers (38.2%; P = 0.024).

DISCUSSION

Similar to the previous study, T. rubrum was found to have the highest prevalence, followed by

T. mentagrophytes complex and M. canis.11 Dermatophyte

TABLE 3. Behavior of owner after the diagnosis of dermatophytosis.

infections transmitted via animals are common. Nowadays, dermatophytosis transmitted by pets and livestock through contact is likely to affect children and young adults.12 Zoophilic dermatophytes are considered to be causative pathogens, especially M. canis, of which cats and dogs are the main reservoirs.12-18 In this study, 92.3% of the patients infected with M. canis owned pets. Among these pets, the majority were reported to be symptomatic, but not all of them. As reported in previous studies, the infected pets could be totally asymptomatic.19 The correlation between zoophilic infections and the factors of sex and age depends on the dermatophyte species and the type of animal, such as a pet or livestock.5,20 Female owners had the highest prevalence of zoophilic dermatophytosis, correlated with previous studies.21 In addition, the more intimacy between patients and their pets, the more chance patients would be infected with zoophilic M. canis, as this current study showed that pet-lovers were significantly closer to their pet than non-pet lovers, and M. canis was also found significantly in them. In the current study, the owners of cats-only had a significantly higher prevalence of M. canis (60.0%) than those with dogs-only (11.4%), with P < 0.001. This corresponds well with the previous study: cats infected by

M. canis caused significant environmental contamination, shedding viable, airborne, fungal elements.16,22 Dogs have been reported to play a lesser role in the environmental spreading of M. canis, contaminating surfaces but never the air.13,23,24

Previous studies have investigated the relationship between causative pathogens and tinea infections.

T. rubrum was found to predominately cause tinea corporis, tinea cruris, and tinea pedis, whereas M. canis commonly caused tinea capitis because exposed areas (such as the scalp, beard, face, and arms) are prone to zoophilic dermatophyte infection.21,25 As with our investigation, those findings demonstrated significant correlations between exposed areas and zoophilic dermatophytosis, and between unexposed areas and anthropophilic dermatophytosis. The research on the human-animal relationship in patients with zoophilic dermatophytosis was limited. Most patients (70.5%) showed no changes in the human-pet relationship after the diagnosis of an animal-transmitted infection. However, the relationship status was influenced by how the patients behaved with their animals. The change in relationship rate for non-pet lovers was significantly lower than those of pet lovers. It may be due to self- awareness and knowledge of the infection in pet-lovers. They had a better understanding of the transmission of zoophilic infections so they kept more distance between themselves and their pets, as shown in the recurrence rate of pet-lovers which was less than non-pet lovers. Therefore, it is essential for patients to be educated that zoophilic dermatophytosis is curable,26 and the level of awareness of animal abandonment should be raised. Treatment of pets by veterinarians is needed because the infected pets are reservoirs of dermatophytes and can spread the infection to both humans and other pets.

The study had several limitations. Firstly, since this was a retrospective chart review, some data were incomplete or derived from recall histories. Secondly, Because T. mentagrophytes complex is a species complex consisting of 5 species, including T. interdigitale as the anthropophilic species and T. mentagrophytes as the zoophilic species, the diagnosis can be ambiguous due to phenotypic variations. The molecular technique that helps to differentiate T. interdigitale from T. mentagrophytes was not routinely used to reveal the identity of the causative species. They were therefore grouped as

T. mentagrophytes complex and were included only in the descriptive analysis of the prevalence of the dermatophyte species. Regarding sample size calculation, it was calculated based on prevalence of zoophilic dermatophytosis among those with dermatophytosis. However, sample size of subgroup population was not evaluated. Finally, fungal cultures from the pets were not obtained to prove the causative relationship.

In summary, the nature of the relationship between the patients and the pets was the chief influence in the type of dermatophytosis. Dermatologists should be aware that zoophilic infections can have a rapid onset and mainly affect the exposed body parts. Although some pets were reported to be asymptomatic, identification of the reservoirs of dermatophytosis is important in the treatment process and helps prevent future recurrence. A close relationship between humans and pets is also an important factor that leads to appropriate pet management after diagnosis of zoophilic dermatophytosis, resulting in good treatment outcomes and minimizing the risk of recurrence.

ACKNOWLEDGMENTS

All authors declare that there were no conflicts of interest. We thank Dr. Chulaluk Komoltri for her statistical advice. We also thank Rungsima Kiratiwongwan, MD and Supisara Wongdama, MD, for their kind support.

Conflicts of interest: None declared

Funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit-sectors.

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2. Craddock LN, SM S. Superficial Fungal Infection. In: Kang S, Amagai M, Bruckner AL, Enk AH, Margolis DJ, McMichael AJ, et al., eds. Fitzpatrick’s Dermatology, 9th ed: McGraw-Hill,

   2019. p. 2927.

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4. Bunyaratavej S, Kiratiwongwan R, Limphoka P, Lertrujiwanit K, Leeyaphan C. Pattern Recognition using Morphologies of Anthropophilic and Zoophilic Dermatophytosis Lesions: Comparison between Final-Year Medical Students and Dermatology Residents. Siriraj Med J 2020;72(6):488-91.

5. Aghamirian MR, Ghiasian SA. Dermatophytoses in outpatients attending the Dermatology Center of Avicenna Hospital in Qazvin, Iran. Mycoses 2008;51(2):155-60.

6. Seebacher C, Bouchara JP, Mignon B. Updates on the epidemiology of dermatophyte infections. Mycopathologia 2008;166(5-6): 335-52.

7. Cai W, Lu C, Li X, Zhang J, Zhan P, Xi L, et al. Epidemiology of Superficial Fungal Infections in Guangdong, Southern China: A Retrospective Study from 2004 to 2014. Mycopathologia 2016;181(5-6):387-95.

8. Rashidian S, Falahati M, Kordbacheh P, Mahmoudi M, Safara M, Sadeghi Tafti H, et al. A study on etiologic agents and clinical manifestations of dermatophytosis in Yazd, Iran. Curr Med Mycol 2015;1(4):20-5.

9. Chermette R, Ferreiro L, Guillot J. Dermatophytoses in animals. Mycopathologia 2008;166(5-6):385-405.

10. Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses 2008;51 Suppl 4:2-15.

11. Bunyaratavej S, Limphoka P, Kiratiwongwan R, Leeyaphan C. Survey of skin and nail fungal infections by subject age among thai adults and the etiological organisms. Southeast Asian J Trop Med Public Health SE 2019;50(6):1118-31.

12. Nenoff P, Handrick W, Krüger C, Vissiennon T, Wichmann K, Gräser Y, et al. Dermatomykosen durch Haus- und Nutztiere. Der Hautarzt 2012;63(11):848-58.

13. Cafarchia C, Romito D, Sasanelli M, Lia R, Capelli G, Otranto D. The epidemiology of canine and feline dermatophytoses in southern Italy. Mycoses 2004;47(11-12):508-13.

14. Halsby KD, Walsh AL, Campbell C, Hewitt K, Morgan D. Healthy animals, healthy people: zoonosis risk from animal contact in pet shops, a systematic review of the literature. PLoS One 2014;9(2): e89309.

15. Katoh T, Maruyama R, Nishioka K, Sano T. Tinea corporis due to Microsporum canis from an asymptomatic dog. J Dermatol 1991;18(6):356-9.

16. Mancianti F, Nardoni S, Corazza M, D’Achille P, Ponticelli C. Environmental detection of Microsporum canis arthrospores in the households of infected cats and dogs. J Feline Med Surg 2003;5(6):323-8.

17. Shiraki Y, Hiruma M, Matsuba Y, Kano R, Makimura K, Ikeda S, et al. A case of tinea corporis caused by Arthroderma benhamiae (teleomorph of Tinea mentagrophytes) in a pet shop employee. J Am Acad Dermatol 2006;55(1):153-4.

18. Stull JW, Peregrine AS, Sargeant JM, Weese JS. Household knowledge, attitudes and practices related to pet contact and associated zoonoses in Ontario, Canada. BMC Public Health 2012;12(1):553.

19. Kobwanthanakun W, Bunyaratavej S, Leeyaphan C. Tinea corporis from Microsporum canis: A case report in 2 patients from 1 asymptomatic feline. Thai J Dermatol 2018;34(4):299- 304.

20. Iorio R, Cafarchia C, Capelli G, Fasciocco D, Otranto D,

    GiangasperoA. Dermatophytoses in cats and humans in central Italy: epidemiological aspects. Mycoses 2007;50(6):491-5.

21. Bunyaratavej S, Limphoka P, Kiratiwongwan R, Leeyaphan C. Comparison of patient and clinical differences between superficial skin infections due to Microsporum canis and Trichophyton rubrum. Southeast Asian J Trop Med Public Health SE 2020;51(1).

22. Limphoka P, Bunyaratavej S, Leeyaphan C. Fingernail onychomycosis caused by Microsporum canis in a teenager. Pediatr Dermatol 2021;38(2):524-5.

23. Cafarchia C, Romito D, Capelli G, Guillot J, Otranto D. Isolation of Microsporum canis from the hair coat of pet dogs and cats belonging to owners diagnosed with M. canis tinea corporis. Vet Dermatol 2006;17(5):327-31.

24. Moriello KA, Coyner K, Paterson S, Mignon B. Diagnosis and treatment of dermatophytosis in dogs and cats.: Clinical Consensus Guidelines of the World Association for Veterinary Dermatology. Vet Dermatol 2017;28(3):266-e68.

25. Ali-Shtayeh MS, Yaish S, Jamous RM, Arda H, Husein EI. Updating the epidemiology of dermatophyte infections in Palestine with special reference to concomitant dermatophytosis. J Mycol Med 2015;25(2):116-22.

26. Bunyaratavej S, Kiratiwongwan R, Suphatsathienkul P, Munprom K, Matthapan L, Supcharoenkul S, et al. Effect of Different Shampoos and Contact Time on Microsporum canis Infected Hair: In vitro Model Study. Thai J Dermatol 2020;36(4):150-6.

Association Between the Level of Inflammation at Each Anatomical Sexual Activity from Gram Staining and Neisseria gonorrhoeae and Chlamydia trachomatis Infections

Kittipoom Chinhiran, M.D.*, Rossaphorn Kittiyaowamarn, M.D.*, Busara Bamrungsak, M.Sc.*, Narissara Yuchui, M.Sc.*, Kornsiri Boonprathueng, B.Sc.*, Natnaree Girdthep, M.Sc.*, Thanyaporn Karnpanich, B.Sc.*, Phichayut Phinyo, M.D., Ph.D.*,***, Pakpoom Wongyikul, M.D.**, Teodora Elvira Wi, M.D.****

*Bangrak STIs Center, Division of AIDS and STIs, Department of Disease Control, Ministry of Public Health, Bangkok, Thailand. **Center for Clinical

Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. ***Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. ****Department of the Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland.

ABSTRACT

Objective: This study aimed to determine the association between the severity of inflammation at each anatomical sexual activity from gram staining with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. Materials and Methods: This study was conducted using laboratory test data from patients at the Bangrak Sexually Transmitted Infections Center. The data obtained consisted of gram staining, which was divided by the number of polymorphonuclear leukocytes (PMNL), NG culture, and Nucleic Acid Amplification Test (NAAT) for NG and CT results.

Results: For the diagnostic association between PMNL and NG infection, the results revealed that samples with urethral PMNL 3+ or 4+ carried a significant likelihood ratio (LR) for positive infection, LR 5.61 (P<0.001) and LR

59.66 (P<0.001), respectively. Cervical, rectal, and pharyngeal PMNL was not related to infection. For CT infection, urethral gram stains with PMNL levels were greater than or equal to 2+ and cervical specimens with PMNL 4+ were associated with CT infection. Rectal and pharyngeal PMNL showed no significant association with CT infection. Conclusion: Determination of PMNL levels from gram staining contributes to the diagnosis of patients with NG and CT in the urethra, particularly for patients with a high degree of inflammation.

Keywords: Gram staining; culture; nucleic acid amplification test; Neisseria gonorrhoeae; Chlamydia trachomatis

(Siriraj Med J 2023; 75: 99-105)

INTRODUCTION

Gonorrhea and nongonococcal urethritis (NGU) are sexually transmitted infections (STIs) that remain major public health problems in many countries around the world. According to an estimation from the World Health Organization in 2020, there will be 374 million

new STIs in all regions around the world, with 82 million being gonorrhea, and 129 million being chlamydia.1

From epidemiological surveillance data in Thailand, it was found that STIs increased the morbidity rate from

28.8 per 100,000 people in 2017 to 33.6 per 100,000 people in 2020, which then slightly decreased to 29.2

Corresponding author: Kittipoom Chinhiran E-mail: x_destiny_war@hotmail.com

Received 5 July 2022 Revised 14 August 2022 Accepted 17 August 2022 ORCID ID:http://orcid.org/0000-0001-8233-0000 https://doi.org/10.33192/smj.v75i2.260747

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

per 100,000 people in 2021. The most common disease was gonorrhea, followed by NGU. In 2021, the rate of gonorrhea was 9.2 per 100,000 people, while NGU was

2.7 per 100,000 people. It was found that the age group that experienced the most STIs comprised those aged 15-24 years.2

Gonorrhea and NGU are STIs that cause inflammation at the site of infection. Gonorrhea is caused by Neisseria gonorrhoeae (NG), while NGU is caused by several types of organisms such as Chlamydia trachomatis (CT), Mycoplasma genitalium, Ureaplasma urealyticum, and Trichomonas vaginalis.3,4 The most common organism that causes NGU is CT.3,5,6 In addition, gonorrhea can also be found in coinfection with other sexually transmitted diseases.5,7 Screening for gonorrhea and NGU can be carried out by gram staining, which can detect pathogens that are gram-negative intracellular diplococci in polymorphonuclear leukocytes (PMNL) in gonorrhea3,8 and PMNL can be detected in both gonorrhea and nongonococcal urethritis.3

Previous studies found that urethral gram staining had sensitivity to the diagnosis of gonorrhea in 95% of symptomatic male patients, with 97% specificity, and cervical gram staining had 40-60% sensitivity.9 The sensitivity of gram staining is reduced in the rectum, pharynx, and in those who are asymptomatic.10 The sensitivity of gram staining in diagnosing chlamydia in males is 23%.11 In females, it was found that using only gram staining had low sensitivity.12

Studies that address the association between the markers of inflammation (i.e. PMNL levels) and NG and CT infections are limited. This study aimed to determine the association between the severity of inflammation from gram staining with NG and CT.

MATERIALS AND METHODS

This study was conducted using laboratory test data

from patients at the Bangrak STIs Center during the period from January 1, 2019, to December 31, 2021. The data were obtained from routine services consisting of gram staining, NG culture, and Nucleic Acid Amplification Test (NAAT) for NG and CT results. The data were obtained with permission from the Division of AIDS and STIs, and the Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP).

The data used for analysis consisted of gram staining results, which were divided by the number of PMNL/ oil immersion field (OIF). They were categorized as no PMNL, rare (1-4 cells/OIF), 1+ (5-10 cells/OIF), 2+ (11-

20 cells/OIF), 3+ (21-40 cells/OIF) and 4+ (≥41 cells/ OIF).13 Results of NG culture and NAAT for NG and CT, which are both standard tests for the diagnosis8 of urethra, cervix, rectum, and pharynx, were collected. Gram staining data that yielded no culture or NAAT results were excluded.

Statistical methods

Data were analyzed using STATA version 17.0. Categorical data were reported as numbers and percentages. Diagnostic accuracy was measured by sensitivity, specificity, likelihood ratio (LR), and area under the receiving operating characteristics (ROC) curve. Confidence intervals for each diagnostic parameter were also estimated at a 95% level. A p-value < 0.05 was considered statistically significant.

RESULTS

Of the 1,474 gram-stained patients, 883 cases were tested for NG by cultures or NAAT and 225 cases were identified as NG infection: urethra (145 cases; 40.7%), cervix (54 cases; 13.8%), rectum (20 cases; 18.5%), pharynx (6 cases; 21.4%); 1,179 cases were tested for CT by NAAT and 431 cases were identified as CT infection: urethra (267 cases; 53.8%), cervix (102 cases; 22.5%), rectum (31

cases; 25.0%), pharynx (31 cases; 29.5%) (Table 1).

Gram stain

Total

samples

Total samples with Positive for Total samples with Positive for

culture/NAAT for NG NG NAAT for CT CT

TABLE 1. Number of samples with NG and CT infections.

Abbreviations: CT, Chlamydia trachomatis; NG, Neisseria gonorrhoeae; NAAT, Nucleic Acid Amplification Test

For the diagnostic association between PMNL and NG infection, our results revealed that samples with urethral PMNL 3+ or 4+ carried a significant likelihood ratio for positive infection, LR 5.61 (95% CI 2.57 to 12.24,

P<0.001) and LR 59.66 (95% CI 25.37 to 140.27, P<0.001),

respectively. At a PMNL cutoff point equal to or more than 3+, the sensitivity and specificity for NG infection were 75.2% (95% CI 67.4 to 82.0) and 95.7% (95% CI

92.1 to 98.0), respectively, whereas the sensitivity and

specificity were 56.5% (95% CI 48.1 to 64.8) and 99.1% (95% CI 96.6 to 99.9), respectively, for a cutoff point at 4+. Cervical, rectal, and pharyngeal PMNL were not related to infection (Table 2).

For CT infection, urethral gram stain with PMNL levels 2+, 3+, and 4+, the LRs were significantly higher than 1 [LR 1.89 (95% CI 1.09 to 3.27, P 0.024) for PMNL 2+,

LR 2.24 (95% CI 1.28 to 3.92, P 0.005) for PMNL 3+, and

LR 6.00 (95% CI 3.02 to 11.91, P <0.001) for PMNL 4+]

TABLE 2. Diagnostic accuracy for the number of PMNL for NG infections.

Abbreviations: AuROC, area under the receiving operating characteristics curve; CI, confidence interval; LR, likelihood ratio; NA, not applicable; NE: not estimable; NG, Neisseria gonorrhoeae; PMNL: polymorphonuclear leukocytes

and, thus, were associated with the infection. At a PMNL cutoff point equal to or more than 2+, the sensitivity was 55.1% (95% CI 48.9 to 61.1), and specificity was 79.9%

(95% CI 74.1 to 84.9). At PMNL 3+, the sensitivity was

38.6. % (95% CI 32.7 to 44.7), and specificity was 88.6%

(95% CI 83.8 to 92.4). At PMNL 4+, sensitivity was

21.0% (95% CI 16.2 to 26.4), and specificity was 96.5%

(95% CI 93.2 to 98.5). In cervical specimens, PMNL 4+ was modestly associated with CT infection, with LR

2.03 (95% CI 1.27 to 3.25, P 0.003). At a PMNL cutoff

point equal to or more than 4+, sensitivity was 33.3% (95%CI 24.3 to 43.4) and specificity was 83.5% (95% CI 79.2 to 87.2) for diagnosis of CT infection. Rectal and pharyngeal PMNL showed no significant association with CT infection (Table 3).

In terms of discriminative ability, only urethral PMNL levels had an area under ROC higher than 0.70, the generally defined acceptable threshold, for both NG and CT infections (Figs 1 and 2).

TABLE 3. Diagnostic accuracy for the number of PMNL for CT infections.

Abbreviations: AuROC, area under the receiving operating characteristics curve; CI, confidence interval; LR, likelihood ratio; NA, not applicable; NE: not estimable; CT Chlamydia trachomatis; PMNL: polymorphonuclear leukocytes

Fig 1. ROC curve for diagnosis of NG from each specimen.

Fig 2. ROC curve for diagnosis of CT from each specimen.

DISCUSSION

Gonorrhea and chlamydia can cause inflammation at the site of the infection. The patient may or may not have symptoms. Screening for inflammation from gram staining can aid in diagnosis and treatment in cases where a culture test or NAAT is not available. The US Center for Disease Control defined PMNL ≥2 WBC/OIF as urethritis and PMNL >10 WBC/high-power field as cervicitis.3 However, some studies used PMNL values

>30 WBC per high-power field for cervicitis.14,15

From this study, the inflammation defined by PMNL from gram staining at the urethra was significantly associated with NG and CT infections. Those infected with NG were associated with higher PMNL levels than those with CT (3+ or above in NG and 2+ or above in CT). Inflammation of the cervix was statistically associated with CT infection at the PMNL level 4+. The severity of anal and pharyngeal inflammation was not associated with NG and CT infection.

Therefore, the detection of inflammation from PMNL levels may help in the diagnosis of gonorrhea and chlamydia in the urethra. The high levels of PMNL will have a relatively high specificity found in urethral and cervical infections, so it can help in the diagnosis of infection at the urethra and cervix. However, it may not be used to aid in the diagnosis of gonorrhea or chlamydia in the rectal and pharyngeal region. However, higher PMNL levels have been found to have low sensitivity, while lower PMNL levels have high sensitivity but low specificity, so other factors such as the patient’s symptoms, and history of sexual behavior should be used to support the diagnosis.

Usually, gonorrhea is diagnosed using culture or NAAT, while chlamydia uses NAAT as the standard test. However, NAAT for chlamydia is not widely used in Thailand due to the high cost. The syndromic management is more common in gonorrhea and will lead to overtreatment which can cause antimicrobial- resistant microorganisms.16 Therefore, it is necessary to step forward the diagnosis of gonorrhea and chlamydia from a syndromic approach to laboratory diagnosis by using at least gram staining which is feasible in all levels of hospitals.

From this study, the cutoff of PMNL from gram staining can be used for decision-making in the diagnosis and treatment of gonorrhea and chlamydia. This will reduce the rate of drug resistance from the overuse of antibiotics.

This study had several limitations. First, the number of rectal and pharyngeal samples was too low to draw rigorous conclusions on the diagnostic association

between PMNL levels and infections. Second, there was no standardized protocol to collect the specimens from all sites from each included patient, and not all patients were verified for both infections. Therefore, we could not accurately estimate the proportion of patients with isolated infection of NG and CT or patients with co-infection from both organisms.

CONCLUSION

The determination of PMNL levels from gram staining contributes to the diagnosis of patients with NG and CT in the urethra, particularly patients with a high degree of inflammation. If the amount of inflammation is lower, however, other factors such as a history of sexual behavior or additional patient symptoms should be considered to support the diagnosis.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the Division of AIDS and STIs, and the Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) for permitting the use of data.

Conflict of interest: none

REFERENCES

1. World Health Organization (WHO) [Internet]. Sexually transmitted infections (STIs); 2021 [cited 2022 Mar 22]. Available from: https://www.who.int/news-room/fact-sheets/detail/ sexually-transmitted-infections-(stis).

2. HIV INFO HUB [Internet]. Rate of five main STIs reported case in Thailand, 2009-2020; 2021 [cited 2022 May 5]. Available from: https://hivhub.ddc.moph.go.th/epidemic.php.

3. Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):51-68.

4. Wada K, Hamasuna R, Sadahira T, Araki M, Yamamoto S. UAA-AAUS guideline for M. genitalium and non-chlamydial non-gonococcal urethritis. J Infect Chemother. 2021;27(10): 1384-8.

5. Bellinato F, Maurelli M, Gisondi P, Fernandez ML, Girolomoni

   G. Clinical profile and co-infections of urethritis in males. Ital J Dermatol Venerol. 2021;156(6):681-5.

6. Mostafa MM, Mahdy A, Ghoniem G. Updates on Sexually Transmitted Urethro-cystitis. Current Bladder Dysfunction Reports. 2022.p.1-6.

7. Surawan TM, Jiamton S. Three Co-Existing Sexually Transmitted Diseases in a Heterosexual Male Youth: A Case Report. Siriraj Med J. 2016;68:117-8.

8. Centers for Disease Control and Prevention. Screening Tests To Detect Chlamydia trachomatis and Neisseria gonorrhoeae Infections 2002. MMWR Recomm Rep. 2002;51(RR-15):6.

9. Unemo M, Ballard R, Ison C, Lewis D, Ndowa F, Peeling R, editors Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus. Geneva: WHO

   Document Production Services; 2013.

10. Meyer T, Buder S. The Laboratory Diagnosis of Neisseria gonorrhoeae: Current Testing and Future Demands. Pathogens. 2020;9(91):1-19.

11. Orellana MA, Gómez-Lus ML, Lora D. Sensitivity of Gram stain in the diagnosis of urethritis in men. Sex Transm Infect. 2012;88:284-7.

12. Myziuk L, Romanowski B, Brown M. Endocervical Gram stain smears and their usefulness in the diagnosis of Chlamydia trachomatis. Sex Transm Inf. 2001;77:103-6.

13. Charoenwattanachokchai A, Lokpichart S, editors. Laboratory Manual for STIs Diagnosis. Nakhon Pathom: National Office of Buddhism; 2010.

14. Randjelovic I, Moghaddam A, De Blasio BF, Moi H. The Role of Polymorphonuclear Leukocyte Counts from Urethra, Cervix, and Vaginal Wet Mount in Diagnosis of Nongonococcal Lower Genital Tract Infection. Infect Dis Obstet Gynecol. 2018; 2018:8236575.

15. De la Tablaa VO, Gutiérrezb F. Cervicitis: Etiology, diagnosis and treatment. Enferm Infecc Microbiol Clin (Engl Ed). 2019;37(10): 661-7.

16. Sirivongrangson P, Girdthep N, Sukwicha W, Buasakul P, Tongtoyai J, Weston E, et al. The first year of the global Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in Bangkok, Thailand, 2015-2016. PLoS One. 2018;13(11): e0206419.

Prevalence and Trend of Photodermatoses in Thailand: A 16-year Retrospective Study at Siriraj Hospital

Surachanee Likittanasombat, M.D.*, Narumol Silpa-archa, M.D.*, Chayada Chaiyabutr, M.D.*, Rattanavalai Nitiyarom, M.D.**, Wanee Wisuthsarewong, M.D.**, Chanisada Wongpraparut, M.D.*

*Department of Dermatology, **Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: Photodermatoses are a group of cutaneous disorders with abnormal reactions triggered by exposure to sunlight. Previous studies reported varying photodermatoses prevalence in Caucasians and African-Americans; however, it was seldom reported in the Asian population. The aim of our study was to determine the prevalence, clinical characteristics and trend of photodermatoses in Thailand.

Materials and Methods: A retrospective chart review was performed at the Faculty of Medicine Siriraj Hospital, Mahidol University using diagnoses from the International Classification of Disease (ICD), Tenth Revisions codes, between January 2005 and September 2021.

Results: A total of 561 patients with definite diagnoses of photodermatoses were identified. The prevalence of photodermatoses in the outpatient dermatology clinic was 3 cases per 1,000. The most common photodermatoses were chemical and drug-induced photosensitivity (39.4%), followed by immunologically-mediated photodermatoses (30.1%), photo-aggravated dermatoses (29.4%) and genophotodermatoses (1.1%). Overall phototesting was performed in 276 cases (49.2%). In our study, some photodermatoses had unique clinical characteristics including a pinpoint popular variant of polymorphous light eruption and adult-onset actinic prurigo. Over 16 years, the trend of patients being diagnosed with photodermatoses has continued to rise gradually with an increment of 1.67 times.

Conclusion: Photodermatoses are uncommon in Thailand. Some photodermatoses have distinctive clinical features in Asian populations. The trend of photodermatoses in Thailand is continually rising, reflecting an increase in physicians’ awareness and knowledge of these cutaneous conditions.

Keywords: Photodermatoses; drug-induced photosensitivity; immunologically-mediated photodermatoses; photo- aggravated dermatoses; genophotodermatoses; polymorphous light eruption (Siriraj Med J 2023; 75: 106-114)

INTRODUCTION

Photodermatoses are a group of skin disorders caused by exposure to sunlight. Photodermatoses are generally classified into four categories: immunologically- mediated photodermatoses, chemical and drug-induced photosensitivity, photoexacerbated dermatoses, and genophotodermatoses.1-3 Immunologically-mediated

photodermatoses are further sub-divided into five diseases: polymorphous light eruption (PMLE), actinic prurigo (AP), chronic actinic dermatitis (CAD), solar urticaria (SU), and hydroa vacciniforme (HV). The pathophysiology of these diseases is still unclear, but it varies depending on different immune dysregulation. Most of these diseases require phototesting to confirm the diagnosis.1,3,4 Chemical

Corresponding author: Chanisada Wongpraparut E-mail: chanisada@hotmail.com

Received 26 June 2022 Revised 23 August 2022 Accepted 30 August 2022 ORCID ID:http://orcid.org/0000-0002-9014-3229 https://doi.org/10.33192/smj.v75i2.260748

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

and drug-induced photosensitivity can be triggered by both external and internal causes. The external causes can be further split into photoallergic and phototoxic reactions. Moreover, various exogenous chemical agents can lead to phytophotodermatitis and photoallergic contact dermatitis. An example of photodermatoses caused by endogenous agents is porphyrias, which are caused by an abnormal heme biosynthetic pathway.1,3 Meanwhile, photoexacerbated dermatoses such as photoexacerbated eczema, photoexacerbated atopic dermatitis, systemic lupus erythematosus, autoimmune connective tissue diseases, vesiculobullous diseases, HIV photosensitivity, are the main groups of photodermatoses.1 Last but not least, genophotodermatoses are rare genetic disorders that cause severe photosensitivity and other manifestations, and examples include xeroderma pigmentosum (XP), Bloom syndrome, and Rothmund–Thomson syndrome.1,2 To diagnose photodermatoses, the history, clinical presentation, phototesting, an laboratory investigations (e.g. porphyrins, lupus serology) are necessary in each individual case. Phototesting can help in evaluating the degree of photosensitivity and the specific wavelength which elicits a cutaneous response in an individual patient.

Moreover, some cases also require a photoprovocation test, photopatch test and skin biopsy.

According to the previous studies, genetics, race, skin phototypes and climate are the factors associated with different prevalence of photodermatoses.5-9 In Europe, the prevalences of immunologically-mediated photodermatoses is reported to be about 10-20% in PMLE,10

16.5 cases per 100,000 for CAD,11 3.9 cases per 100,000 for solar urticaria,11 and 3.3 cases per 100,000 for actinic prurigo.11 Most of previous studies have been conducted on the African-American and Caucasian populations.7-9,11 Proportion of photodermatoses was also different between races. PMLE has more prevalence in Africans-Americans and Caucasians compared to other races. Drug-induced photosensitivity and photo-aggravated dermatoses are more prevalent in Caucasians.9 However, the research that looks at the overall proportion of photodermatoses in the Thai population is still limited. Determining the prevalence, clinical features, and trend of photodermatoses in Thailand was the purpose of this study.

MATERIALS AND METHODS

This study was approved by the ethics committee of the Siriraj Institutional Review Board (COA no. Si 909/2021). A 16-year retrospective chart review was performed at the Faculty of Medicine Siriraj Hospital, Mahidol University, a tertiary care hospital in Thailand, using diagnoses from the International Classification of Disease

(ICD), Tenth Revisions codes related to photodermatoses between January 2005 and September 2021. In our study, cases of photodermatoses were selected if the diagnosis included one of the following ICD-10 codes: E52 (Niacin deficiency [pellagra]), E80 (Disorders of porphyrin and bilirubin metabolism), E80.0 (Hereditary erythropoietic porphyria), E80.1 (Porphyria cutanea tarda), E80.2 (Other porphyria), L29.9 (Actinic prurigo), L56.0 (Drug phototoxic response), L56.1 (Drug photoallergic response), L56.2 (Photocontact dermatitis [berloque dermatitis])., L56.3 (Solar urticaria), L56.4 (Polymorphous light eruption), L56.8 (Photoallergic contact dermatitis), L57.8 (Chronic actinic dermatitis), Q82.1 (Xeroderma pigmentosum), Q82.88 (Other specified congenital malformations of skin) and Q87.1 (Congenital malformation syndromes predominantly associated with short stature). All medical records were manually reviewed. The data were collected and included patients’ clinical chart data upon further investigations correlated with the ICD code. Phototesting with or without photoprovocation test was required in the diagnoses of immunologically-mediated photodermatoses. Photopatch test was required in the diagnosis of photoallergic contact dermatitis. Diagnosis of porphyrias was made based on clinical presentations and porphyrin profiles. Other photodermatoses can be diagnosed by clinical presentation, phototesting with or without photoprovocation. The exclusion criteria were patients whose clinical history and examination were not suggestive of photodermatoses. Demographic data including age, sex, age onset of skin lesions, skin phototype, photosensitizing agents, area of skin involvement and characteristics of skin lesions were collected. Additional investigations such as phototesting, photoprovocation test, photopatch test, skin biopsy and laboratory investigations were also recorded.

Phototesting by determination of minimal erythema dose (MED) for UVA and UVB was performed on the lower back areas or the buttocks. UVA radiation was delivered by UVA 700 L (Herbert Waldmann GmbH & Co. KG, Villingen-Schwenningen, Germany); UVB radiation was delivered by a bank of UV 802 L (Herbert Waldmann GmbH & Co. KG, Villingen-Schwenningen, Germany); and visible light delivered for 30 minutes by a Kodak Carousel S-AV 2020 projector (Kodak AG, Stuttgart, Germany). For the visible light testing, a glass of water was placed in front of the projector to absorb infrared. Another visible light machine included the Fiber-Lite Mi-152 High Intensity Illuminator (Dolan- Jenner industries, Boxborough, MA, USA). An IL1700 radiometer (International light Inc. Newburyport, MA, USA) was used to measure UVA and UVB irradiance.

Minimal Erythema Dose was defined as the lowest UV dose which produced perceptible erythema reading at 24 hours after UVA and UVB irradiation. The result will be interpreted as UVA and UVB photosensitivity if the MED-UVA < 30 J/cm2 and MED-UVB < 50 mJ/cm2.

The photoprovocation test was done to reproduce skin lesions if the phototest was negative but still clinically related to photodermatoses using an energy of 60- 100 J/cm2 of UVA and 1.5 times MED of UVB for 3 consecutive days. Results of the photoprovocation test were measured at 24, 48 and 72 hours. Our photoallergen set used for photopatch testing in this study was developed in accordance with previous literature of photoallergic contact dermatitis. It is mainly composed of ultraviolet filters, topical medications, fragrances and preservatives. Both sets were removed after 48 hours but one set was irradiated with UVA 10 J/cm2. Results were interpreted at 48 and 96 hours.

Statistical analysis

Descriptive analysis was used for demographic data presented as frequency and percentage, or as a mean with standard deviation (SD) and median with interquartile range (IQR). Statistical analysis was carried out using a statistical software (SPSS version 18.0; SPSS Inc., Chicago, USA).

RESULTS

A total of 4,371 medical records matching ICD10 codes from the dermatology clinic were collected and a chart review was performed. Our study confirmed the diagnosis of 561 patients with photodermatoses out of

a total of 189,806 cases who had visited the dermatology clinic from 2005-2021. The calculated prevalence of photodermatoses in our hospital was 3 cases per 1,000. Of the 561 cases, the majority were females (n=335, 59.7%). The mean age ± SD and mean age to onset ± SD of photodermatoses was 49.1±17.8 years and 47.9±18.4 years, respectively. The median disease duration was 4 months (0.75, 12.0). The majority of patients had skin type IV and V. The most frequently affected areas in photodermatoses were the extensor surface of the upper extremities (n=362, 64.8%), face (n=255, 45.5%) and the V-shape of the neck (n=231, 41.3%). Meanwhile, papules and plaques (n=297, 52.9%), macules and patches (n=254, 45.3%) and wheals and flares (n=29, 5.2%) were the most commonly reported. Examples of photo-distributed lesions are shown in Fig 1. Overall, phototesting, photoprovocation, and photopatch tests were conducted in 276 (49.2%), 37 (6.6%) and 43 (7.7%) patients, respectively. Of the 276 patients who underwent phototesting, positive results were seen in 148 (53.6%) patients. Most of the cases with positive phototesting results were diagnosed with CAD (n=53, 35.8%), SU (n=27, 18.2%) and AP (n=17, 11.5%). The details of photodermatoses, phototesting, photoprovocation, and photopatch test results are summarized in Table 1.

Immunologically-mediated photodermatoses

Of 561 photodermatoses patients, 169 (30.1%) patients were diagnosed with immunologically-mediated photodermatoses. CAD (n=67, 11.9%) was the most prevalent followed by AP (n=38, 6.8%), PMLE (n=35, 6.2%) and SU (n=29, 5.2%). No cases of HV were found.

Fig 1. Skin lesions on photodistributed areas.

Original Article SMJ

Porphyria cutanea tarda

Erythropoietic protoporphyria

12 (2.1%)

1 (0.2%)

-

1#

-

-

-

-

-

-

-

-

-

-

TABLE 1. Prevalence and photobiological characteristics of each photodermatoses (N=561).